The Experts below are selected from a list of 25659 Experts worldwide ranked by ideXlab platform
Christopher D Anderson - One of the best experts on this subject based on the ideXlab platform.
-
Lymphopenia infectious complications and outcome in spontaneous intracerebral hemorrhage
Neurocritical Care, 2017Co-Authors: Andrea Morotti, Sandro Marini, Michael J Jessel, Kristin Schwab, Christina Kourkoulis, Alison M Ayres, Edip M Gurol, Anand Viswanathan, Steven M Greenberg, Christopher D AndersonAbstract:Background Lymphopenia is increasingly recognized as a consequence of acute illness and may predispose to infections. We investigated whether admission Lymphopenia (AL) is associated with increased risk of infectious complications and poor outcome in patients with spontaneous intracerebral hemorrhage (ICH).
-
Abstract TP326: Lymphopenia, Infectious Complications and Outcome in Spontaneous Intracerebral Hemorrhage
Stroke, 2017Co-Authors: Andrea Morotti, Sandro Marini, Michael J Jessel, Kristin Schwab, Christina Kourkoulis, Alison M Ayres, Edip M Gurol, Anand Viswanathan, Steven M Greenberg, Christopher D AndersonAbstract:Background and Purpose: Lymphopenia is increasingly recognized as a consequence of acute illness and may predispose to infections. We investigated whether admission Lymphopenia (AL) is associated with increased risk of infectious complications and poor outcome in patients with spontaneous intracerebral hemorrhage (ICH). Methods: we analyzed a prospectively collected cohort of ICH patients ascertained between 1994 and 2015. Subjects were included if they had a lymphocyte count obtained within 24 h from onset and AL was defined as lymphocyte count
Crystal L. Mackall - One of the best experts on this subject based on the ideXlab platform.
-
Harnessing the physiology of Lymphopenia to support adoptive immunotherapy in lymphoreplete hosts
Blood, 2009Co-Authors: Hua Zhang, Joanna L. Meadors, Rita Poon, Martin Guimond, Crystal L. MackallAbstract:Lymphopenia enhances the effectiveness of adoptive immunotherapy by facilitating expansion of transferred T cells but also limits the T-cell repertoire available to mediate immune responses and, in humans, is associated with chronic immune dysfunction. Previous studies concluded that Lymphopenia augments adoptive immunotherapy by diminishing Tregs and increasing homeostatic cytokines. We sought to determine whether targeted therapies that replicate the physiology of Lymphopenia in lymphoreplete hosts could provide a similarly supportive milieu. Pmel-1 T cells were transferred to B16-bearing lymphopenic versus lymphoreplete mice receiving αCD25 and/or recombinant human interleukin-7. Although CD25-based Treg depletion was inefficient because of peripheral expansion of CD4+CD25−FOXP3+ cells, outcomes were better in αCD25-treated lymphoreplete hosts than in lymphopenic hosts, and adoptive immunotherapy was most effective in lymphoreplete hosts receiving αCD25 plus recombinant human interleukin-7. Lymphopenic hosts supported increased proliferation of adoptively transferred antigen-specific T cells, but cells transferred to lymphoreplete recipients receiving targeted therapies showed superior function. Further, determinant spreading was substantial in lymphoreplete hosts but absent in lymphopenic hosts. These results demonstrate that targeted therapies delivered to mimic the “physiology of Lymphopenia” enhance the efficacy of adoptive immunotherapy in lymphoreplete hosts and provide a potentially superior alternative to the induction of Lymphopenia.
-
autoimmunity during Lymphopenia a two hit model
Clinical Immunology, 2006Co-Authors: Tom Krupica, Crystal L. MackallAbstract:Abstract The immune system has evolved elaborate mechanisms to respond to diverse antigens while minimizing the risk for autoimmune reactivity. During Lymphopenia, however, some mechanisms that normally serve to maintain host tolerance are temporarily suspended. Peripheral T cells proliferate in response to self-antigens in lymphopenic hosts, but proliferation toward these same antigens is prevented when T cell numbers are normal. This process, termed homeostatic peripheral expansion, augments peripheral T cell number and limits repertoire skewing during recovery from Lymphopenia and also predisposes lymphopenic hosts to autoimmune disease. This paper reviews murine and human settings in which autoimmunity occurs in the context of Lymphopenia. We propose a two-hit model, in which Lymphopenia plus another insult is sufficient to induce autoimmune disease. Among the secondary insults that appear sufficient to induce autoimmunity during Lymphopenia are overproduction of IL-21 as occurs in the NOD.SCID mouse, depletion of Tregs as demonstrated in murine colitis and gastritis models, and tissue inflammation as seen in HIV infected patients who develop immune reconstitution inflammatory syndrome (IRIS). Delineating critical cofactors which result in autoimmune disease during Lymphopenia can provide insight into the pathophysiology of naturally occurring autoimmune diseases as well as generating testable hypothesis for inducing tumor-specific autoimmunity in lymphopenic hosts with cancer.
-
neonates support Lymphopenia induced proliferation
Immunity, 2003Co-Authors: Rebecca S Mchugh, Crystal L. Mackall, Gregory D Sempowski, Gilles Foucras, William E PaulAbstract:Abstract T cells expand without intentional antigen stimulation when transferred into adult lymphopenic environments. In this study, we show that the physiologic lymphopenic environment existing in neonatal mice also supports CD4 T cell proliferation. Strikingly, naive CD4 T cells that proliferate within neonates acquire the phenotypic and functional characteristics of memory cells. Such proliferation is inhibited by the presence of both memory and naive CD4 T cells, is enhanced by 3-day thymectomy, is independent of IL-7, and requires a class II MHC-TCR interaction and a CD28-mediated signal. CD44 bright CD4 T cells in neonates have a wide repertoire as judged by the distribution of Vβ expression. Thus, Lymphopenia-induced T cell proliferation is a physiologic process that occurs during the early postnatal period.
Marta Calbet - One of the best experts on this subject based on the ideXlab platform.
-
the sphingosine 1 phosphate receptor 1 antagonist w146 causes early and short lasting peripheral blood Lymphopenia in mice
International Immunopharmacology, 2011Co-Authors: Gema Tarrason, Mariona Auli, Sanam Mustafa, Vladislav Dolgachev, Maria Teresa Domenech, Neus Prats, Maria Dominguez, Rosa Lopez, Nuria Aguilar, Marta CalbetAbstract:Agonists of the sphingosine-1-phosphate (S1P) receptors, like fingolimod (FTY720), are a novel class of immunomodulators. Administration of these compounds prevents the egress of lymphocytes from primary and secondary lymphoid organs causing peripheral blood Lymphopenia. Although it is well established that Lymphopenia is mediated by S1P receptor type 1 (S1P1), the exact mechanism is still controversial. The most favored hypothesis states that S1P1 agonists cause internalization and loss of the cell surface receptor on lymphocytes, preventing them to respond to S1P. Hence, S1P1 agonists would behave in vivo as functional antagonists of the receptor. For this hypothesis to be valid, a true S1P1 antagonist should also induce Lymphopenia. However, it has been reported that S1P1 antagonists fail to show this effect, arguing against the concept. Our study demonstrates that a S1P1 antagonist, W146, induces a significant but transient blood Lymphopenia in mice and a parallel increase in CD4+ and CD8+ lymphocytes in lymph nodes. Treatment with W146 also causes the accumulation of mature T cells in the medulla of the thymus and moreover, it induces lung edema. We show that both the S1P1 antagonist and a S1P1 agonist cause Lymphopenia in vivo in spite of their different effects on receptor expression in vitro. Although the antagonist purely blocks the receptor and the agonist causes its disappearance from the cell surface, the response to the endogenous ligand is prevented in both cases. Our results support the hypothesis that Lymphopenia evoked by S1P1 agonists is due to functional antagonism of S1P1 in lymphocytes.
Leo Lefrancois - One of the best experts on this subject based on the ideXlab platform.
-
cell surface residence of sphingosine 1 phosphate receptor 1 on lymphocytes determines lymphocyte egress kinetics
Journal of Experimental Medicine, 2010Co-Authors: Shobha Thangada, Kamal M Khanna, Victoria A Blaho, Myat Lin Oo, Dongsoon Im, Leo LefrancoisAbstract:The sphingosine 1-phosphate receptor 1 (S1P1) promotes lymphocyte egress from lymphoid organs. Previous work showed that agonist-induced internalization of this G protein–coupled receptor correlates with inhibition of lymphocyte egress and results in Lymphopenia. However, it is unclear if S1P1 internalization is necessary for this effect. We characterize a knockin mouse ( S1p1rS5A/S5A ) in which the C-terminal serine-rich S1P1 motif, which is important for S1P1 internalization but dispensable for S1P1 signaling, is mutated. T cells expressing the mutant S1P1 showed delayed S1P1 internalization and defective desensitization after agonist stimulation. Mutant mice exhibited significantly delayed Lymphopenia after S1P1 agonist administration or disruption of the vascular S1P gradient. Adoptive transfer experiments demonstrated that mutant S1P1 expression in lymphocytes, rather than endothelial cells, facilitated this delay in Lymphopenia. Thus, cell-surface residency of S1P1 on T cells is a primary determinant of lymphocyte egress kinetics in vivo.
Andrea Morotti - One of the best experts on this subject based on the ideXlab platform.
-
Lymphopenia infectious complications and outcome in spontaneous intracerebral hemorrhage
Neurocritical Care, 2017Co-Authors: Andrea Morotti, Sandro Marini, Michael J Jessel, Kristin Schwab, Christina Kourkoulis, Alison M Ayres, Edip M Gurol, Anand Viswanathan, Steven M Greenberg, Christopher D AndersonAbstract:Background Lymphopenia is increasingly recognized as a consequence of acute illness and may predispose to infections. We investigated whether admission Lymphopenia (AL) is associated with increased risk of infectious complications and poor outcome in patients with spontaneous intracerebral hemorrhage (ICH).
-
Abstract TP326: Lymphopenia, Infectious Complications and Outcome in Spontaneous Intracerebral Hemorrhage
Stroke, 2017Co-Authors: Andrea Morotti, Sandro Marini, Michael J Jessel, Kristin Schwab, Christina Kourkoulis, Alison M Ayres, Edip M Gurol, Anand Viswanathan, Steven M Greenberg, Christopher D AndersonAbstract:Background and Purpose: Lymphopenia is increasingly recognized as a consequence of acute illness and may predispose to infections. We investigated whether admission Lymphopenia (AL) is associated with increased risk of infectious complications and poor outcome in patients with spontaneous intracerebral hemorrhage (ICH). Methods: we analyzed a prospectively collected cohort of ICH patients ascertained between 1994 and 2015. Subjects were included if they had a lymphocyte count obtained within 24 h from onset and AL was defined as lymphocyte count
