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Jay A. Levy - One of the best experts on this subject based on the ideXlab platform.

  • Discovery of another anti-HIV protein in the search for the CD8+ Cell anti-HIV Factor.
    Proceedings of the National Academy of Sciences of the United States of America, 2015
    Co-Authors: Jay A. Levy
    Abstract:

    Nearly three decades ago, soon after the recognition of AIDS and its causative agent, HIV, the first immune response against the AIDS virus was identified: an unexpected anti-HIV activity of CD8+ Cells that did not involve Cell killing (1). This immune response differed from the classic CD8+ Cell antiviral activity in which cytotoxic T lymphocytes kill virus-infected Cells (2). The CD8+ Cell noncytotoxic anti-HIV response (CNAR) became evident in HIV-infected individuals who were healthy without any clinical signs but had serologic evidence of HIV infection. Although, initially, these asymptomatic individuals were expected to develop AIDS, several continued to remain healthy. Later it was determined that it takes about 10 y for 50% of infected individuals to develop AIDS (3). From these, about 5–8% are asymptomatic long-term survivors (LTS) with normal CD4+ Cells and low plasma viral loads (4, 5). CNAR was discovered when the peripheral blood mononuclear Cells from the LTS were placed in culture and only released infectious virus when the CD8+ Cells were removed. Adding back the CD8+ Cells to the infected CD4+ Cells inhibited virus replication without affecting the viability of the CD4+ Cells (1).

  • Nevirapine inhibits the anti-HIV activity of CD8+ Cells.
    Journal of acquired immune deficiency syndromes (1999), 2013
    Co-Authors: Lianxing Liu, Lin Wang, Liusheng Huang, Vincent Siu, Fernando Teque, Francesca T. Aweeka, Jay A. Levy
    Abstract:

    Antiretroviral therapy (ART) significantly reduced the CD8+ Cell non-cytotoxic anti-HIV response (CNAR) in twelve HIV-1-infected subjects (p < 0.0001). In separate experiments, CD8+ Cells from long term survivors (LTS) were co-cultured with HIV-infected CD4+ Cells using varying concentrations of anti-HIV drugs. The antiviral function of CD8+ Cells from four of fourteen LTS was reduced with exposure to 10µM nevirapine (p < 0.05). The antiviral activity of CD8+ Cells from two LTS was inhibited by 5µM zidovudine. These studies indicate that nevirapine and probably zidovudine can inhibit the anti-HIV activity of CD8+ Cells and thus could influence the effectiveness of ART.

  • VCAM-1 expression on CD8+ Cells correlates with enhanced anti-HIV suppressing activity.
    Journal of immunology (Baltimore Md. : 1950), 2005
    Co-Authors: Leyla S. Diaz, Hillary Foster, Mars Stone, Sue Fujimura, David A. Relman, Jay A. Levy
    Abstract:

    CD8 + Cells from HIV-infected individuals showing the CD8 + Cell noncytotoxic antiviral response unexpectedly revealed mRNA for VCAM-1, a Cell surface molecule found on endothelial Cells. Uninfected subjects had undetectable levels of VCAM-1 mRNA in their CD8 + Cells. Flow cytometry analysis showed that up to 12% of the CD8 + Cells from HIV-positive individuals expressed VCAM-1 compared with 0.8% of the CD8 + Cells of HIV-negative individuals. Enrichment of the CD8 + VCAM-1 + Cell population and subsequent coculture with CD4 + Cells acutely infected with HIV-1 showed that the VCAM-1 + CD8 + Cells were able to suppress viral replication with 50% less input Cells than the unseparated CD8 + Cell population. This study demonstrates, for the first time, the expression of VCAM-1 on CD8 + Cells. Moreover, the CD8 + VCAM-1 + Cells show enhanced CD8 + Cell noncytotoxic antiviral response activity that could have clinical importance in HIV infection.

  • Mature dendritic Cells can enhance CD8+ Cell noncytotoxic anti-HIV responses: the role of IL-15.
    Blood, 2003
    Co-Authors: Joann C. Castelli, Elaine K. Thomas, Michel Gilliet, Yong-jun Liu, Jay A. Levy
    Abstract:

    The CD8+ Cell noncytotoxic anti-HIV response (CNAR) is associated with a long-term healthy clinical state in HIV-infected individuals. Over time CNAR is reduced concomitant with progression to disease. In studies to evaluate whether the interaction between CD8+ Cells and dendritic Cells (DCs) could increase CNAR, CD8+ Cells from individuals who showed a decrease in this antiviral activity were cocultured with monocyte-derived dendritic Cells matured with CD40 ligand. After coculture with these mature DCs, the CD8+ Cells showed an increase in CNAR greater than that observed with CD8+ Cells costimulated with CD3/CD28 antibodies. This antiviral response appeared to be mediated primarily by production of interleukin-15 (IL-15) by the mature DCs. Purified IL-15 also enhanced CNAR, whereas IL-12 showed no substantial effect. These studies provide another potential approach by which the immune system in HIV infection could be restored by cytokine therapy, particularly IL-15 administration. (Blood. 2004;103:2699-2704)

  • alpha-Defensins can have anti-HIV activity but are not CD8 Cell anti-HIV factors.
    AIDS (London England), 2003
    Co-Authors: Carl E Mackewicz, Jun Yuan, Patti Tran, Leyla S. Diaz, Elizabeth C. Mack, Michael E. Selsted, Jay A. Levy
    Abstract:

    BACKGROUND CD8 T Cells from healthy HIV-infected individuals inhibit HIV replication in infected CD4 T Cells by a non-cytotoxic mechanism mediated by a soluble CD8 Cell antiviral factor, CAF. Recently, the antimicrobial peptides, alpha-defensins, were reported to constitute CAF. OBJECTIVE To examine the antiviral activity of alpha-defensins and address their potential role in CD8 Cell non-cytotoxic antiviral responses. DESIGN AND METHODS A purified mixture of human neutrophil proteins (HNP) 1-3 (alpha-defensins) was used to examine the effect of alpha-defensins on HIV virions and on HIV replication in CD4 Cells treated prior to or post infection. alpha-Defensin expression was analyzed at the RNA and protein level in CD8 Cells as well as in various other Cell types. Antibodies to the defensins were tested for their ability to inhibit CAF activity in CD8 Cell culture fluids. RESULTS The alpha-defensins exhibited anti-HIV activity on at least two levels: directly inactivating virus particles; and affecting the ability of target CD4 Cells to replicate the virus. However, while we could demonstrate alpha-defensins in neutrophils and monocytes, we found no evidence for the production of these peptides by CD8 T Cells. No messenger RNA encoding these proteins was detected in purified CD8 T Cells, nor did these Cells produce intraCellular or extraCellular alpha-defensin peptides. Moreover, antibodies specific for human alpha-defensins 1, 2, and 3 did not block the antiviral activity of CAF-active CD8 Cell culture fluids. CONCLUSIONS The alpha-defensins are not produced by CD8 Cells but unexpectedly were found to be expressed in monocytes. alpha-Defensins can have anti-HIV activity but are not CD8 Cell antiviral factors.

Michael F. Tosi - One of the best experts on this subject based on the ideXlab platform.

Janis V Giorgi - One of the best experts on this subject based on the ideXlab platform.

  • shortened telomeres in the expanded cd28 CD8 Cell subset in hiv disease implicate replicative senescence in hiv pathogenesis
    AIDS, 1996
    Co-Authors: Rita B Effros, Richard C Allsopp, Choypik Chiu, Mary Ann Hausner, Karim F Hirji, Lili Wang, Calvin B Harley, Bryant Villeponteau, Michael D West, Janis V Giorgi
    Abstract:

    Objective : To test the hypothesis that the expanded population of non-proliferative CD28- CD8+ T Cells in HIV disease have shortened telomeres, thereby providing evidence that increased rounds of CD8+ Cell division occur during HIV disease, possibly leading to replicative senescence and exhaustion of CD8+ T-Cell responses. Design : CD8+ Cells play a central role in control of HIV infection. In late HIV disease, an expanded population of CD28- CD8+ Cells with reduced proliferative potential has been documented. A similar population of CD28- CD8+ Cells has been identified in ageing humans, where telomere length measurements have suggested that these Cells have reached the irreversible state of replicative senescence. Methods : CD8+ Cells from HIV-infected and control subjects were sorted by flow cytometry into CD28+ and CD28- fractions. Telomere lengths were determined as mean terminal restriction fragment (TRF) lengths by Southern hybridization. Results : The TRF lengths of sorted CD28- CD8+ Cells in HIV-infected subjects ranged between 5 and 7 kilobases (kb) and were significantly shorter than TRF lengths of CD28- CD8+ Cells in uninfected subjects (P= 0.003). TheTRF length in CD28- CD8+ Cells from HIV-infected subjects was the same as that observed for centenarian peripheral blood mononuclear Cells and is compatible with a state of replicative senescence. Conclusions : The shortened telomeres in the CD28- CD8+ Cells in HIV-infected subjects and the poor proliferative potential of these Cells identifies CD8+ Cell replicative senescence as a newly described feature of HIV disease. Our results provide a mechanism for the loss of CD8+ Cell control of viral replication that accompanies advanced HIV disease. Replicative senescence may contribute to exhaustion of the T-Cell response as a result of chronic HIV disease. Whether this phenomenon occurs in other chronic viral infections is unknown.

  • CD8 lymphocyte activation at human immunodeficiency virus type 1 seroconversion development of hla dr cd38 CD8 Cells is associated with subsequent stable cd4 Cell levels
    The Journal of Infectious Diseases, 1994
    Co-Authors: Janis V Giorgi, John Ferbas, Karim F Hirji, Lance E Hultin, Hongnerng Ho, Chencheng Chou, Sheryl Orourke, Lawrence P Park, Joseph B Margolick, John P Phair
    Abstract:

    : Subsets of activated CD8+ lymphocytes defined by membrane expression of the activation antigens HLA-DR and CD38 were counted by three-color flow cytometry in homosexual men who subsequently became seropositive for human immunodeficiency virus type 1 (HIV). Profound CD8+ Cell activation was seen in all subjects at seroconversion and 6 and 12 months later. The HLA-DR+ CD38+ CD8+ Cell population, which has potent direct HIV cytotoxic T Cell activity, was markedly elevated at seroconversion in all subjects. In some men, these levels remained elevated throughout the first year of infection. During the next 5 years, these men had stable CD4+ Cell levels, whereas the others did not. Long-term survivors (seropositive for 9 years, > 800 CD4+ Cells/mm3) also had elevated levels of this subset, despite few other activated CD8+ Cells. Thus, selective elevation of HLA-DR+ CD38- CD8+ Cells was a marker of subsequent stable HIV disease.

  • elevated levels of cd38 CD8 t Cells in hiv infection add to the prognostic value of low cd4 t Cell levels results of 6 years of follow up the los angeles center multicenter aids cohort study
    Journal of Acquired Immune Deficiency Syndromes, 1993
    Co-Authors: Janis V Giorgi, Zhiyuan Liu, Lance E Hultin, William G Cumberland, K Hennessey, Roger Detels
    Abstract:

    A cohort of 98 HIV-infected initially AIDS-free homosexual men from the Multicenter AIDS Cohort Study (MACS) was followed for 6 years to investigate whether CD8+ Cell subsets have prognostic value for progression to AIDS. In the present study, four subsets of CD8+ T Cells that previously have been shown to be selectively elevated in HIV-infected asymptomatic persons, specifically the CD8+ T Cell subsets that were CD38+, HLA-DR+, CD57+ and L-selectin negative (Leu8-), were measured. Forty-nine of the 98 developed AIDS. Prognostic value of these CD8+ Cell subsets was evaluated using the proportional hazards model. Levels of both CD38+ CD8+ and Leu8- CD8+ Cells individually had prognostic value for progression to AIDS. In contrast, CD57+ CD8+ and HLA-DR+ CD8+ Cell subsets levels did not have prognostic value. After adjustment for level of CD4+ T Cells, however, only the elevation in the CD38+ CD8+ Cell subset had additional prognostic value. These results suggest that the level of CD38+ CD8+ Cells could be used together with the CD4+ T Cell level to more accurately predict progression to AIDS among HIV-infected men. These results provide further support for the observation that dramatic and progressive activation of CD8+ T Cells in HIV infection occurs. The power of elevated levels of the CD38+ CD8+ subset to predict poor prognosis in this cohort suggests these CD8+ T Cells reflect an immune stimulation that is ultimately unable to control disease progression.

Xiqing Yue - One of the best experts on this subject based on the ideXlab platform.

  • a recombinant polypeptide from velvet antler of cervus nippon temminck exhibits similar immunomodulatory effects as its natural counterpart
    Immunopharmacology and Immunotoxicology, 2016
    Co-Authors: Enhui Zha, Li Danda, Tiezhong Zhou, Gao Shenyang, Xiqing Yue
    Abstract:

    AbstractContext: Velvet antler (VA) is recognized as one of the most important Chinese traditional medical herbs. To date, the immunoactivity of the single component of VA is rarely studied though its compound extracts have been well analyzed.Objective: The current study was designed to evaluate the immunomodulatory effects of a recombinant polypeptide (rVAP32) based on the VA of the sika deer by comparison with its natural counterpart (nVAP32).Materials and methods: Splenocytes proliferation and NK-Cell cytotoxicity assay was evaluated by the WST-8 colorimetric method. CD4+/CD8+ Cell subpopulations regulation was screened by the flowcytometry method and the Th1 or Th2-related cytokine production was measured by ELISA.Results: In vitro tests showed that both rVAP32 and nVAP32 could significantly stimulate splenocytes proliferation and enhance the NK-Cell cytotoxicity and CD4+/CD8+ Cell subpopulations when compared with the irrelevant peptide and blank control groups. Also, they demonstrated a significant ...

  • immunomodulatory effects of a 3 2kda polypeptide from velvet antler of cervus nippon temminck
    International Immunopharmacology, 2013
    Co-Authors: Enhui Zha, Xuesong Guo, Shenyang Gao, Xiqing Yue
    Abstract:

    The objective of this study was to evaluate the immunomodulatory effects of a native 3.2kDa polypeptide of velvet antler from sika deer (nVAP32) on BALB/c mice immunocytes. In vitro tests showed that nVAP32 significantly stimulated splenocyte proliferation and enhanced the NK cytotoxicity and CD4(+)/CD8(+) Cell subpopulations. Also, nVAP32 demonstrated a significant capacity in up- and down-regulating the expression of Th1- and Th2-related cytokines respectively. These results indicated that nVAP32 might have potential immunomodulatory effects on the immune system of mice and the further investigation on in vivo effects is qualified.

Robert Hostoffer - One of the best experts on this subject based on the ideXlab platform.