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Douglas A. Jabs - One of the best experts on this subject based on the ideXlab platform.
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Autoimmune Th2-Mediated Dacryoadenitis in MRL/MpJ Mice Becomes Th1-Mediated in IL-4 Deficient MRL/MpJ Mice
2015Co-Authors: Douglas A. Jabs, Robert A. Prendergast, Adam L. Campbell, Bella Lee, Hervé C. Gérard, Alan P. Hudson, Karamursel Akpek, Judith A. Whittum-hudsonAbstract:Purpose—MRL/MpJ mice of substrains MRL/MpJ-fas+/fas+ (MRL/+) and MRL/MpJ-faslpr/ faslpr (MRL/lpr) spontaneously develop autoimmune Dacryoadenitis and sialadenitis and are a model for the human disorder Sjögren syndrome. The Dacryoadenitis in both substrains appears to be Th2 in nature, with little IFN-γ and substantial IL-4 at the site of lacrimal gland inflammation. Methods—MRL/MpJ mice with a defective IL-4 gene—both MRL/+-IL-4tm/IL-4tm (MRL/+/ IL-4tm) and MRL/lpr-IL-4tm/IL-4tm (MRL/lpr-IL-4tm)—that resulted in a loss of IL-4 production were bred and evaluated for Dacryoadenitis. Results—MRL/+/IL-4tm and MRL/lpr/IL-4tm mice developed Dacryoadenitis of similar onset, appearance, and severity as found in MRL/MpJ mice with an intact IL-4 gene. Immunohistochemistry examination revealed a substantially greater number of inflammatory cells staining for IFN-γ than for IL-13 in the Dacryoadenitis of IL-4 – deficient MRL/MpJ mice (MRL/+/IL-4tm, 66 % vs. 0.8%, P = 0.001; MRL/lpr/IL-4tm, 67 % vs. 1.2%, P = 0.002). Real-time PCR demonstrated greater amounts of IFN-γ than IL-13 mRNA relative transcripts in lacrimal glands of MRL/lpr/IL-4tm mice (mean difference, 28.6; P = 0.035). Greater CD86 (B7–2) than CD80 (B7–1) expression was present i
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Autoimmune Th2-Mediated Dacryoadenitis in MRL/MpJ Mice Becomes Th1-Mediated in IL-4 Deficient MRL/MpJ Mice
2013Co-Authors: Douglas A. Jabs, Robert A. Prendergast, Adam L. Campbell, Bella Lee, Esen Karamursel Akpek, Hervé C. Gérard, Alan P. Hudson, Judith A. Whittum-hudsonAbstract:PURPOSE. MRL/MpJ mice of substrains MRL/MpJ-fas � /fas � (MRL/�) and MRL/MpJ-fas lpr /fas lpr (MRL/lpr) spontaneously develop autoimmune Dacryoadenitis and sialadenitis and are a model for the human disorder Sjögren syndrome. The Dacryoadenitis in both substrains appears to be Th2 in nature, with little IFN- � and substantial IL-4 at the site of lacrimal gland inflammation. METHODS. MRL/MpJ mice with a defective IL-4 gene—both MRL/�-IL-4 tm /IL-4 tm (MRL/�/IL-4 tm) and MRL/lpr-IL-4 tm /IL-4 tm (MRL/lpr-IL-4 tm)—that resulted in a loss of IL-4 production were bred and evaluated for Dacryoadenitis. RESULTS. MRL/�/IL-4 tm and MRL/lpr/IL-4 tm mice developed Dacryoadenitis of similar onset, appearance, and severity as found in MRL/MpJ mice with an intact IL-4 gene. Immunohistochemistr
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Autoimmune Th2-Mediated Dacryoadenitis in MRL/MpJ Mice Becomes Th1-Mediated in IL-4 Deficient MRL/MpJ Mice
Investigative Opthalmology & Visual Science, 2007Co-Authors: Douglas A. Jabs, Robert A. Prendergast, Adam L. Campbell, Bella Lee, Esen Karamursel Akpek, Hervé C. Gérard, Alan P. Hudson, Judith A. Whittum-hudsonAbstract:Purpose MRL/MpJ mice of substrains MRL/MpJ-fas+/fas+ (MRL/+) and MRL/MpJ-faslpr/faslpr (MRL/lpr) spontaneously develop autoimmune Dacryoadenitis and sialadenitis and are a model for the human disorder Sjogren syndrome. The Dacryoadenitis in both substrains appears to be Th2 in nature, with little IFN-γ and substantial IL-4 at the site of lacrimal gland inflammation.
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autoimmune th2 mediated Dacryoadenitis in mrl mpj mice becomes th1 mediated in il 4 deficient mrl mpj mice
Investigative Ophthalmology & Visual Science, 2007Co-Authors: Douglas A. Jabs, Robert A. Prendergast, Adam L. Campbell, Bella Lee, Esen Karamursel Akpek, Hervé C. Gérard, Alan P. Hudson, Judith A WhittumhudsonAbstract:Purpose MRL/MpJ mice of substrains MRL/MpJ-fas+/fas+ (MRL/+) and MRL/MpJ-faslpr/faslpr (MRL/lpr) spontaneously develop autoimmune Dacryoadenitis and sialadenitis and are a model for the human disorder Sjogren syndrome. The Dacryoadenitis in both substrains appears to be Th2 in nature, with little IFN-γ and substantial IL-4 at the site of lacrimal gland inflammation.
Austin K Mircheff - One of the best experts on this subject based on the ideXlab platform.
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Long-term topical cyclosporine treatment improves tear production and reduces keratoconjunctivitis in rabbits with induced autoimmune Dacryoadenitis.
Journal of Ocular Pharmacology and Therapeutics, 2009Co-Authors: Padmaja B. Thomas, Z Zhu, Douglas Stevenson, Joel E Schechter, Austin K Mircheff, D. M. Samant, S. Selvam, Yanru Wang, Sang W. Song, Samuel C. YiuAbstract:Abstract Purpose: To use a rabbit model of induced autoimmune Dacryoadenitis to evaluate the efficacy of topical ophthalmic cyclosporine A (CsA). Methods: Autoimmune Dacryoadenitis was induced by injecting autologous peripheral blood lymphocytes, which had been activated in a mixed cell reaction with acinar cells isolated from one inferior lacrimal gland (LG), back into the donor animal's remaining inferior LG. Schirmer's test, tear breakup time, and rose Bengal staining were assessed. Animals with established disease were treated topically with either CsA or Endura twice daily for 5 months. Results: Without treatment tear production and tear stability were abnormal for 6 months, and clear signs of ocular surface defects were evident. Severe immune cell infiltration was observed in the LG. Long-term CsA treatment increased tear production only slightly, but the severity of LG histopathology decreased noticeably. CD4+ T-cell infiltration of the LG was decreased and infiltration by MHC class II-expressing c...
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tumor necrosis factor inhibitor gene expression suppresses lacrimal gland immunopathology in a rabbit model of autoimmune Dacryoadenitis
Cornea, 2003Co-Authors: Z Zhu, Douglas Stevenson, Joel E Schechter, Austin K Mircheff, Robert W Crow, Roscoe Atkinson, Thomas Ritter, Swaraj Bose, Melvin D TrousdaleAbstract:Purpose. To evaluate the effect of tumor necrosis factor (TNF) inhibitor protein on lacrimal gland immunopathology and ocular surface disease resulting from induced Dacryoadenitis. Methods. Autoimmune Dacryoadenitis was induced in rabbits by injecting the lacrimal glands with peripheral blood lymphocytes (PBLs) activated by 5 days of coculture with autologous acinar cells in a mixed cell reaction. In the treated group, an adenoviral vector carrying the TNF inhibitor gene (AdTNFRp55-Ig) was concurrently injected with AMCR-PBL. Tear production was monitored by Schirmer test, and tears were collected for detection of TNF-inhibitor protein. Frozen sections of the glands were immunostained for expression of CD4, CD8, rabbit thymic lymphocyte antigen (RTLA), and CD18. Histological sections of lacrimal glands were examined using the TUNEL technique to monitor apoptosis. Results. Soluble TNF-inhibitor protein was detected by ELISA in tears, with titers at a maximum on day 3, declining by day 7, and undetectable by day 14. Tear production declined in the induced Dacryoadenitis group but did not change when glands had been treated with AdTNFRp55-Ig simultaneously with disease induction. Tear break-up time and rose bengal staining properties were not altered by treatment. Fourteen days after the glands were injected with activated PBLs, focal mononuclear cell infiltrates were observed around ducts and venules, some of which assumed the high endothelial phenotype, and between acini. Immune cells in the infiltrates stained positive for CD4, RTLA, and CD18. Glands that received AdTNFRp55-Ig concurrently with activated PBLs had decreased numbers of CD4 cells, CD18 cells, RTLA, and apoptotic cells. Conclusions. In vivo transduction of the lacrimal gland with AdTNFRIp55-Ig resulted in transient expression in the gland and the appearance of TNF-inhibitor protein in tears. The presence of soluble TNF-inhibitor protein partially suppressed the appearance of Sjogren's syndrome-like features of reduced tear production and the immunohistopathology associated with induced autoimmune Dacryoadenitis but not tear break-up time and ocular surface disease. This may reflect immunoregulation in the lacrimal gland but not in the conjunctiva.
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Lacrimal histopathology and ocular surface disease in a rabbit model of autoimmune Dacryoadenitis.
Cornea, 2003Co-Authors: Z Zhu, Douglas Stevenson, Joel E Schechter, Austin K Mircheff, Atkinson R, TrousdaleAbstract:Purpose. To study the effects of induced autoimmune Dacryoadenitis on lacrimal gland function, histopathology, and ocular surface disease in a rabbit model. Methods. One lacrimal gland was surgically excised from each experimental rabbit, and epithelial cells were purified, cultured, irradiated, and then cocultured with autologous peripheral blood lymphocytes (PBLs) for 5 days. Autoimmune Dacryoadenitis was induced by injecting the autologous mixed cell reactions (AMCRs) into the rabbit's remaining lacrimal gland. Normal rabbits and rabbits with both lacrimal glands injected with nonstimulated PBLs were examined as controls. Eyes were evaluated biweekly for 8 weeks by slit-lamp biomicroscopy, Schirmer testing, tear break-up time measurement, and rose bengal examination. Sections of lacrimal glands removed at 8 weeks post-operation were immunostained using antibodies against rabbit class II major histocompatibility complex molecule (MHC-II), CD4, CD8, CD 18, and rabbit thymic lymphocyte antigen (RTLA). Relative numbers of positively stained cells were quantified with a ChromaVision image analysis system. Results. During an 8-week period, a continuous decrease in tear production and stability, accompanied by a continuous increase in rose bengal staining, occurred in eyes in which AMCR-PBL had been injected into the ipsilateral lacrimal glands. Similar, though generally less severe, changes occurred in eyes contralateral to the AMCR-PBL-injected eyes. No obvious changes by 8 weeks in these parameters were found in eyes in which the lacrimal glands had been injected with nonstimulated PBLs or in the lacrimal gland-excised eyes contralateral to normal eyes. Interstitial cells in normal lacrimal glands expressed CD18 and RTLA antigens, but few expressed CD4, CD8, or MHC-II. Focal mononuclear cell infiltrates were only found in lacrimal glands from animals with induced autoimmune Dacryoadenitis. These cells were predominantly positive for CD4 (7.3-fold increase), RTLA (7.8-fold increase), or CD18 (42-fold increase). MHC-II expression in interstitial and ductal epithelial cells was also significantly greater in these animals than in control animals. The mononuclear cell infiltrates were frequently found enveloping venules, some of which appeared to be high endothelial cell venules. The ductal epithelium also contained CD4 and CD8 immunopositivity, within the epithelium, at the lumenal surface, or surrounding the ducts. Occasionally CD4 and CD8 immunopositive cells could be identified within the acinar lumens. Conclusions. Injection of activated PBLs (i.e., AMCR-PBLs) in the lacrimal gland induces autoimmune Dacryoadenitis with immunopathologic features similar to those of Sjogren's syndrome. The lacrimal immunopathology is accompanied by typical clinical manifestations of dry eye syndrome. The persistent significant dry eye does not appear to result just from failure of the diseased gland but from a more general dysfunction of the surface secretory tissues.
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autologous lacrimal lymphoid mixed cell reactions induce Dacryoadenitis in rabbits
Experimental Eye Research, 2000Co-Authors: Zhijun Guo, Joel E Schechter, Austin K Mircheff, Donghong Song, Ana Maria Azzarolo, Dwight W. Warren, Richard L. Wood, Harvey R. KaslowAbstract:Autoimmune Dacryoadenitis, such as occurs in Sjogren's syndrome, is a frequent cause of lacrimal insufficiency, which in turn can cause dry eye. Rabbits are used frequently to test ocular therapies. Our goal is to develop a rabbit model of autoimmune Dacryoadenitis to identify and test candidate therapies. Our approach arises from the observations that lacrimal gland epithelial cells stimulate proliferation in cultured autologous lymphocyte preparations and that an anti-MHC II antibody blocks this proliferation. The purpose of this study was to determine if injecting this proliferating autologous mixed cell reaction could induce Dacryoadenitis in rabbits. After establishing that irradiated lacrimal gland epithelial cells stimulate proliferation in autologous peripheral blood lymphocytes, irradiated cells from a single lacrimal gland were co-cultured with autologous lymphocytes and after 5 days the mixed cell reaction, or components of the reaction, were injected into the contralateral lacrimal gland of the donor rabbit. After 2 weeks, the injected glands were removed and lymphocytic infiltration quantitated using digital image analysis of immunostained histological sections. Injecting an autologous mixed cell reaction of co-cultured irradiated lacrimal gland epithelial cells and lymphocytes reliably induced abundant periductal foci of >200 lymphocytes expressing CD18 and/or a rabbit thymic lymphocyte antigen (RTLA). Injection of medium or autologous lymphocytes alone elicited little response; injections of lymphocytes cultured with lysates of lacrimal gland epithelial cells elicited variable, modest responses. These lysates did not stimulate proliferation in the mixed cell reaction and proliferation was not observed if a porous membrane separated co-cultured lacrimal gland cells and lymphocytes. The results demonstrate that injecting an autologous mixed cell reaction of lacrimal gland epithelial cells and lymphocytes reliably creates a model of autoimmune Dacryoadenitis. The relative ineffectiveness of components of the reaction to do the same supports the hypothesis that lacrimal gland epithelial cells trigger or exacerbate lacrimal autoimmune disease by presentation of autoantigens via MHC II. This experimental system can aid efforts to further understand mechanisms of diseases, and to identify and test candidate therapies.
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Autologous Lacrimal–Lymphoid Mixed-cell Reactions Induce Dacryoadenitis in Rabbits
Experimental Eye Research, 2000Co-Authors: Zhijun Guo, Joel E Schechter, Austin K Mircheff, Donghong Song, Ana Maria Azzarolo, Dwight W. Warren, Richard L. Wood, Harvey R. KaslowAbstract:Autoimmune Dacryoadenitis, such as occurs in Sjogren's syndrome, is a frequent cause of lacrimal insufficiency, which in turn can cause dry eye. Rabbits are used frequently to test ocular therapies. Our goal is to develop a rabbit model of autoimmune Dacryoadenitis to identify and test candidate therapies. Our approach arises from the observations that lacrimal gland epithelial cells stimulate proliferation in cultured autologous lymphocyte preparations and that an anti-MHC II antibody blocks this proliferation. The purpose of this study was to determine if injecting this proliferating autologous mixed cell reaction could induce Dacryoadenitis in rabbits. After establishing that irradiated lacrimal gland epithelial cells stimulate proliferation in autologous peripheral blood lymphocytes, irradiated cells from a single lacrimal gland were co-cultured with autologous lymphocytes and after 5 days the mixed cell reaction, or components of the reaction, were injected into the contralateral lacrimal gland of the donor rabbit. After 2 weeks, the injected glands were removed and lymphocytic infiltration quantitated using digital image analysis of immunostained histological sections. Injecting an autologous mixed cell reaction of co-cultured irradiated lacrimal gland epithelial cells and lymphocytes reliably induced abundant periductal foci of >200 lymphocytes expressing CD18 and/or a rabbit thymic lymphocyte antigen (RTLA). Injection of medium or autologous lymphocytes alone elicited little response; injections of lymphocytes cultured with lysates of lacrimal gland epithelial cells elicited variable, modest responses. These lysates did not stimulate proliferation in the mixed cell reaction and proliferation was not observed if a porous membrane separated co-cultured lacrimal gland cells and lymphocytes. The results demonstrate that injecting an autologous mixed cell reaction of lacrimal gland epithelial cells and lymphocytes reliably creates a model of autoimmune Dacryoadenitis. The relative ineffectiveness of components of the reaction to do the same supports the hypothesis that lacrimal gland epithelial cells trigger or exacerbate lacrimal autoimmune disease by presentation of autoantigens via MHC II. This experimental system can aid efforts to further understand mechanisms of diseases, and to identify and test candidate therapies.
Joel E Schechter - One of the best experts on this subject based on the ideXlab platform.
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Long-term topical cyclosporine treatment improves tear production and reduces keratoconjunctivitis in rabbits with induced autoimmune Dacryoadenitis.
Journal of Ocular Pharmacology and Therapeutics, 2009Co-Authors: Padmaja B. Thomas, Z Zhu, Douglas Stevenson, Joel E Schechter, Austin K Mircheff, D. M. Samant, S. Selvam, Yanru Wang, Sang W. Song, Samuel C. YiuAbstract:Abstract Purpose: To use a rabbit model of induced autoimmune Dacryoadenitis to evaluate the efficacy of topical ophthalmic cyclosporine A (CsA). Methods: Autoimmune Dacryoadenitis was induced by injecting autologous peripheral blood lymphocytes, which had been activated in a mixed cell reaction with acinar cells isolated from one inferior lacrimal gland (LG), back into the donor animal's remaining inferior LG. Schirmer's test, tear breakup time, and rose Bengal staining were assessed. Animals with established disease were treated topically with either CsA or Endura twice daily for 5 months. Results: Without treatment tear production and tear stability were abnormal for 6 months, and clear signs of ocular surface defects were evident. Severe immune cell infiltration was observed in the LG. Long-term CsA treatment increased tear production only slightly, but the severity of LG histopathology decreased noticeably. CD4+ T-cell infiltration of the LG was decreased and infiltration by MHC class II-expressing c...
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tumor necrosis factor inhibitor gene expression suppresses lacrimal gland immunopathology in a rabbit model of autoimmune Dacryoadenitis
Cornea, 2003Co-Authors: Z Zhu, Douglas Stevenson, Joel E Schechter, Austin K Mircheff, Robert W Crow, Roscoe Atkinson, Thomas Ritter, Swaraj Bose, Melvin D TrousdaleAbstract:Purpose. To evaluate the effect of tumor necrosis factor (TNF) inhibitor protein on lacrimal gland immunopathology and ocular surface disease resulting from induced Dacryoadenitis. Methods. Autoimmune Dacryoadenitis was induced in rabbits by injecting the lacrimal glands with peripheral blood lymphocytes (PBLs) activated by 5 days of coculture with autologous acinar cells in a mixed cell reaction. In the treated group, an adenoviral vector carrying the TNF inhibitor gene (AdTNFRp55-Ig) was concurrently injected with AMCR-PBL. Tear production was monitored by Schirmer test, and tears were collected for detection of TNF-inhibitor protein. Frozen sections of the glands were immunostained for expression of CD4, CD8, rabbit thymic lymphocyte antigen (RTLA), and CD18. Histological sections of lacrimal glands were examined using the TUNEL technique to monitor apoptosis. Results. Soluble TNF-inhibitor protein was detected by ELISA in tears, with titers at a maximum on day 3, declining by day 7, and undetectable by day 14. Tear production declined in the induced Dacryoadenitis group but did not change when glands had been treated with AdTNFRp55-Ig simultaneously with disease induction. Tear break-up time and rose bengal staining properties were not altered by treatment. Fourteen days after the glands were injected with activated PBLs, focal mononuclear cell infiltrates were observed around ducts and venules, some of which assumed the high endothelial phenotype, and between acini. Immune cells in the infiltrates stained positive for CD4, RTLA, and CD18. Glands that received AdTNFRp55-Ig concurrently with activated PBLs had decreased numbers of CD4 cells, CD18 cells, RTLA, and apoptotic cells. Conclusions. In vivo transduction of the lacrimal gland with AdTNFRIp55-Ig resulted in transient expression in the gland and the appearance of TNF-inhibitor protein in tears. The presence of soluble TNF-inhibitor protein partially suppressed the appearance of Sjogren's syndrome-like features of reduced tear production and the immunohistopathology associated with induced autoimmune Dacryoadenitis but not tear break-up time and ocular surface disease. This may reflect immunoregulation in the lacrimal gland but not in the conjunctiva.
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Lacrimal histopathology and ocular surface disease in a rabbit model of autoimmune Dacryoadenitis.
Cornea, 2003Co-Authors: Z Zhu, Douglas Stevenson, Joel E Schechter, Austin K Mircheff, Atkinson R, TrousdaleAbstract:Purpose. To study the effects of induced autoimmune Dacryoadenitis on lacrimal gland function, histopathology, and ocular surface disease in a rabbit model. Methods. One lacrimal gland was surgically excised from each experimental rabbit, and epithelial cells were purified, cultured, irradiated, and then cocultured with autologous peripheral blood lymphocytes (PBLs) for 5 days. Autoimmune Dacryoadenitis was induced by injecting the autologous mixed cell reactions (AMCRs) into the rabbit's remaining lacrimal gland. Normal rabbits and rabbits with both lacrimal glands injected with nonstimulated PBLs were examined as controls. Eyes were evaluated biweekly for 8 weeks by slit-lamp biomicroscopy, Schirmer testing, tear break-up time measurement, and rose bengal examination. Sections of lacrimal glands removed at 8 weeks post-operation were immunostained using antibodies against rabbit class II major histocompatibility complex molecule (MHC-II), CD4, CD8, CD 18, and rabbit thymic lymphocyte antigen (RTLA). Relative numbers of positively stained cells were quantified with a ChromaVision image analysis system. Results. During an 8-week period, a continuous decrease in tear production and stability, accompanied by a continuous increase in rose bengal staining, occurred in eyes in which AMCR-PBL had been injected into the ipsilateral lacrimal glands. Similar, though generally less severe, changes occurred in eyes contralateral to the AMCR-PBL-injected eyes. No obvious changes by 8 weeks in these parameters were found in eyes in which the lacrimal glands had been injected with nonstimulated PBLs or in the lacrimal gland-excised eyes contralateral to normal eyes. Interstitial cells in normal lacrimal glands expressed CD18 and RTLA antigens, but few expressed CD4, CD8, or MHC-II. Focal mononuclear cell infiltrates were only found in lacrimal glands from animals with induced autoimmune Dacryoadenitis. These cells were predominantly positive for CD4 (7.3-fold increase), RTLA (7.8-fold increase), or CD18 (42-fold increase). MHC-II expression in interstitial and ductal epithelial cells was also significantly greater in these animals than in control animals. The mononuclear cell infiltrates were frequently found enveloping venules, some of which appeared to be high endothelial cell venules. The ductal epithelium also contained CD4 and CD8 immunopositivity, within the epithelium, at the lumenal surface, or surrounding the ducts. Occasionally CD4 and CD8 immunopositive cells could be identified within the acinar lumens. Conclusions. Injection of activated PBLs (i.e., AMCR-PBLs) in the lacrimal gland induces autoimmune Dacryoadenitis with immunopathologic features similar to those of Sjogren's syndrome. The lacrimal immunopathology is accompanied by typical clinical manifestations of dry eye syndrome. The persistent significant dry eye does not appear to result just from failure of the diseased gland but from a more general dysfunction of the surface secretory tissues.
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autologous lacrimal lymphoid mixed cell reactions induce Dacryoadenitis in rabbits
Experimental Eye Research, 2000Co-Authors: Zhijun Guo, Joel E Schechter, Austin K Mircheff, Donghong Song, Ana Maria Azzarolo, Dwight W. Warren, Richard L. Wood, Harvey R. KaslowAbstract:Autoimmune Dacryoadenitis, such as occurs in Sjogren's syndrome, is a frequent cause of lacrimal insufficiency, which in turn can cause dry eye. Rabbits are used frequently to test ocular therapies. Our goal is to develop a rabbit model of autoimmune Dacryoadenitis to identify and test candidate therapies. Our approach arises from the observations that lacrimal gland epithelial cells stimulate proliferation in cultured autologous lymphocyte preparations and that an anti-MHC II antibody blocks this proliferation. The purpose of this study was to determine if injecting this proliferating autologous mixed cell reaction could induce Dacryoadenitis in rabbits. After establishing that irradiated lacrimal gland epithelial cells stimulate proliferation in autologous peripheral blood lymphocytes, irradiated cells from a single lacrimal gland were co-cultured with autologous lymphocytes and after 5 days the mixed cell reaction, or components of the reaction, were injected into the contralateral lacrimal gland of the donor rabbit. After 2 weeks, the injected glands were removed and lymphocytic infiltration quantitated using digital image analysis of immunostained histological sections. Injecting an autologous mixed cell reaction of co-cultured irradiated lacrimal gland epithelial cells and lymphocytes reliably induced abundant periductal foci of >200 lymphocytes expressing CD18 and/or a rabbit thymic lymphocyte antigen (RTLA). Injection of medium or autologous lymphocytes alone elicited little response; injections of lymphocytes cultured with lysates of lacrimal gland epithelial cells elicited variable, modest responses. These lysates did not stimulate proliferation in the mixed cell reaction and proliferation was not observed if a porous membrane separated co-cultured lacrimal gland cells and lymphocytes. The results demonstrate that injecting an autologous mixed cell reaction of lacrimal gland epithelial cells and lymphocytes reliably creates a model of autoimmune Dacryoadenitis. The relative ineffectiveness of components of the reaction to do the same supports the hypothesis that lacrimal gland epithelial cells trigger or exacerbate lacrimal autoimmune disease by presentation of autoantigens via MHC II. This experimental system can aid efforts to further understand mechanisms of diseases, and to identify and test candidate therapies.
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Autologous Lacrimal–Lymphoid Mixed-cell Reactions Induce Dacryoadenitis in Rabbits
Experimental Eye Research, 2000Co-Authors: Zhijun Guo, Joel E Schechter, Austin K Mircheff, Donghong Song, Ana Maria Azzarolo, Dwight W. Warren, Richard L. Wood, Harvey R. KaslowAbstract:Autoimmune Dacryoadenitis, such as occurs in Sjogren's syndrome, is a frequent cause of lacrimal insufficiency, which in turn can cause dry eye. Rabbits are used frequently to test ocular therapies. Our goal is to develop a rabbit model of autoimmune Dacryoadenitis to identify and test candidate therapies. Our approach arises from the observations that lacrimal gland epithelial cells stimulate proliferation in cultured autologous lymphocyte preparations and that an anti-MHC II antibody blocks this proliferation. The purpose of this study was to determine if injecting this proliferating autologous mixed cell reaction could induce Dacryoadenitis in rabbits. After establishing that irradiated lacrimal gland epithelial cells stimulate proliferation in autologous peripheral blood lymphocytes, irradiated cells from a single lacrimal gland were co-cultured with autologous lymphocytes and after 5 days the mixed cell reaction, or components of the reaction, were injected into the contralateral lacrimal gland of the donor rabbit. After 2 weeks, the injected glands were removed and lymphocytic infiltration quantitated using digital image analysis of immunostained histological sections. Injecting an autologous mixed cell reaction of co-cultured irradiated lacrimal gland epithelial cells and lymphocytes reliably induced abundant periductal foci of >200 lymphocytes expressing CD18 and/or a rabbit thymic lymphocyte antigen (RTLA). Injection of medium or autologous lymphocytes alone elicited little response; injections of lymphocytes cultured with lysates of lacrimal gland epithelial cells elicited variable, modest responses. These lysates did not stimulate proliferation in the mixed cell reaction and proliferation was not observed if a porous membrane separated co-cultured lacrimal gland cells and lymphocytes. The results demonstrate that injecting an autologous mixed cell reaction of lacrimal gland epithelial cells and lymphocytes reliably creates a model of autoimmune Dacryoadenitis. The relative ineffectiveness of components of the reaction to do the same supports the hypothesis that lacrimal gland epithelial cells trigger or exacerbate lacrimal autoimmune disease by presentation of autoantigens via MHC II. This experimental system can aid efforts to further understand mechanisms of diseases, and to identify and test candidate therapies.
Yasuhiro Kon - One of the best experts on this subject based on the ideXlab platform.
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bxsb mpj yaa mice develop autoimmune Dacryoadenitis with the appearance of inflammatory cell marker messenger rnas in the lacrimal fluid
Clinical and Experimental Ophthalmology, 2013Co-Authors: Keigo Kosenda, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro KonAbstract:BACKGROUND Dacryoadenitis is characteristic of an autoimmune exocrinopathy, e.g. Sjogren syndrome. We pathologically examined the lacrimal glands of autoimmune-prone BXSB/MpJ-Yaa mice for the appearance of pathological signs of Dacryoadenitis progression in autoimmune Dacryoadenitis models, particularly focusing on messenger RNAs in the lacrimal fluid. METHODS The lacrimal glands of the BXSB/MpJ-Yaa and C57BL/6 mice were histopathologically analyzed in parallel with the evaluation of lacrimation and messenger RNA expression of water channels (Aqp3, Aqp4 and Aqp5). In addition, autoimmune model mice (MRL/MpJ-lpr/lpr and NZB/NZWF1) were used for evaluating cell infiltration and detecting inflammatory cell marker messenger RNAs (Cd68, Ptprc and Cd3e) in the lacrimal fluids by polymerase chain reaction-based methods. RESULTS B-cell predominant lymphocytic infiltrations and the destruction of acini were observed in the lacrimal glands of BXSB/MpJ-Yaa mice. There was no significant difference in the quantity of lacrimal fluid between the BXSB/MpJ-Yaa and C57BL/6 mice. In the BXSB/MpJ-Yaa mice, Aqp3 expression increased significantly with the cell infiltration score, whereas expression of Aqp4 and Aqp5 tended to decrease. Aqp3 expression increased significantly with the cell infiltration score in BXSB/MpJ-Yaa mice. Among inflammatory cell markers, Cd68 was more frequently detected in the lacrimal fluid of the BXSB/MpJ-Yaa, MRL/MpJ-lpr/lpr and NZB/NZWF1 mice than in that of the C57BL/6 mice. CONCLUSION BXSB/MpJ-Yaa mice clearly developed autoimmune Dacryoadenitis. The altered expression of water channels in lacrimal glands might be associated with the preservation of lacrimal fluid excretion in BXSB/MpJ-Yaa mice. The detection of inflammatory cell markers in lacrimal fluid could be used as a diagnostic marker for autoimmune Dacryoadenitis.
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BXSB/MpJ-Yaa mice develop autoimmune Dacryoadenitis with the appearance of inflammatory cell marker messenger RNAs in the lacrimal fluid.
Clinical & Experimental Ophthalmology, 2013Co-Authors: Keigo Kosenda, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro KonAbstract:BACKGROUND Dacryoadenitis is characteristic of an autoimmune exocrinopathy, e.g. Sjogren syndrome. We pathologically examined the lacrimal glands of autoimmune-prone BXSB/MpJ-Yaa mice for the appearance of pathological signs of Dacryoadenitis progression in autoimmune Dacryoadenitis models, particularly focusing on messenger RNAs in the lacrimal fluid. METHODS The lacrimal glands of the BXSB/MpJ-Yaa and C57BL/6 mice were histopathologically analyzed in parallel with the evaluation of lacrimation and messenger RNA expression of water channels (Aqp3, Aqp4 and Aqp5). In addition, autoimmune model mice (MRL/MpJ-lpr/lpr and NZB/NZWF1) were used for evaluating cell infiltration and detecting inflammatory cell marker messenger RNAs (Cd68, Ptprc and Cd3e) in the lacrimal fluids by polymerase chain reaction-based methods. RESULTS B-cell predominant lymphocytic infiltrations and the destruction of acini were observed in the lacrimal glands of BXSB/MpJ-Yaa mice. There was no significant difference in the quantity of lacrimal fluid between the BXSB/MpJ-Yaa and C57BL/6 mice. In the BXSB/MpJ-Yaa mice, Aqp3 expression increased significantly with the cell infiltration score, whereas expression of Aqp4 and Aqp5 tended to decrease. Aqp3 expression increased significantly with the cell infiltration score in BXSB/MpJ-Yaa mice. Among inflammatory cell markers, Cd68 was more frequently detected in the lacrimal fluid of the BXSB/MpJ-Yaa, MRL/MpJ-lpr/lpr and NZB/NZWF1 mice than in that of the C57BL/6 mice. CONCLUSION BXSB/MpJ-Yaa mice clearly developed autoimmune Dacryoadenitis. The altered expression of water channels in lacrimal glands might be associated with the preservation of lacrimal fluid excretion in BXSB/MpJ-Yaa mice. The detection of inflammatory cell markers in lacrimal fluid could be used as a diagnostic marker for autoimmune Dacryoadenitis.
John K C Chan - One of the best experts on this subject based on the ideXlab platform.
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ocular adnexal lymphoma associated with igg4 chronic sclerosing Dacryoadenitis a previously undescribed complication of igg4 related sclerosing disease
The American Journal of Surgical Pathology, 2008Co-Authors: Wah Cheuk, Hunter K L Yuen, Alexander C L Chan, Leeyung Shih, Yanfai Lo, Waikong Chan, John K C ChanAbstract:IgG4-related sclerosing disease is a recently recognized inflammatory lesion frequently involving pancreas, submandibular gland, lacrimal gland, and lymph node. We report 3 cases of ocular adnexal lymphoma arising in IgG4-related chronic sclerosing Dacryoadenitis, a phenomenon that has not been prev