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Peripheral Expansion (peripheral + expansion)
Selected AbstractsVasoactive intestinal peptide induces regulatory T cells during experimental autoimmune encephalomyelitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2006Amelia Fernandez-Martin Abstract CD4+CD25+ regulatory T cells (Treg) control the immune response to a variety of antigens, including self-antigens. Several models support the idea of the peripheral generation of CD4+CD25+ Treg from CD4+CD25, T cells. Little is known about the endogenous factors and mechanisms controlling the peripheral expansion of CD4+CD25+ Treg. In this study we report on the capacity of the vasoactive intestinal peptide (VIP), an immunosuppressive neuropeptide, to induce functional Treg in vivo during the development of experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model. The administration of VIP to EAE mice results in the expansion of the CD4+CD25+, Foxp3-expressing T cells in the periphery and the nervous system, which inhibit encephalitogenic T cell activation. In addition to the increase in the number of CD4+CD25+ Treg, VIP induces more efficient suppressors on a per cell basis. The VIP-generated CD4+CD25+ Treg transfer suppression and significantly ameliorate the progression of the disease. [source] Immune Reconstitution Following Rabbit Antithymocyte GlobulinAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010S. Gurkan Depletional induction therapies are routinely used to prevent acute rejection and improve transplant outcome. The effects of depleting agents on T-cell subsets and subsequent T-cell reconstitution are incompletely defined. We used flow cytometry to examine the effects of rabbit antithymocyte globulin (rATG) on the peripheral T-cell repertoire of pediatric and adult renal transplant recipients. We found that while rATG effectively depleted CD45RA+CD27+ naïve and CD45RO+CD27+ central memory CD4+ T cells, it had little effect on CD45RO+CD27, CD4+ effector memory or CD45RA+CD31,, CD45RO+CD27+ and CD45RO+CD27, CD8+ T cell subsets. When we performed a kinetic analysis of CD31+ recent thymic emigrants and CD45RA+/RO+ T cells, we found evidence for both thymopoiesis and homeostatic proliferation contributing to immune reconstitution. We additionally examined the impact of rATG on peripheral CD4+Foxp3+ T cells. We found that in adults, administration of rATG-induced peripheral expansion and new thymic emigration of T cells with a Treg phenotype, while CD4+Foxp3+ T cells of thymic origin predominated in children, providing the first evidence that rATG induces Treg in vivo. Collectively our data indicate that rATG alters the balance of regulatory to memory effector T cells posttransplant, providing an explanation for how it positively impacts transplant outcome. [source] The number of human peripheral blood CD4+ CD25high regulatory T cells increases with ageCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2005R. Gregg Summary Ageing is associated with evidence of immune deficiency and dysregulation. Key changes in the immune system with ageing include a progressive reduction in naive T cell output associated with thymic involution and peripheral expansion of oligoclonal memory T cells. These features are associated with evidence of impaired immune responsiveness both in vitro and in vivo, termed immune senescence. CD4+ CD25+ T cells have recently been recognized as mediators of peripheral immune regulation and play a role in the control of autoimmune and pathogen-specific immune responses. The significance of CD4+ CD25+ regulatory T cells in the context of immunosenescence is not known. We have investigated the number, phenotype and function of CD4+ CD25+ T cells in healthy volunteers over a wide age range. We demonstrate that the number of CD4+ CD25+ and CD4+ CD25high T cells in healthy volunteers increases with age. In both age groups CD4+ CD25+ T cells showed a phenotype consistent with that described for regulatory T cells. Further analysis of CD4+ CD25high T cells in young and elderly donors showed equivalent expression of intracellular CTLA-4 and surface expression of activation markers. In vitro, functional titration assays of CD4+ CD25high T cells demonstrated equivalent regulatory function in both young and elderly donors, with suppression of proliferation and cytokine production in response to polyclonal T cell stimulation. These observations demonstrate an increase in peripheral blood CD4+ CD25high regulatory T cells associated with ageing. The relevance of these expanded cells in relation to the immune senescence seen in the elderly as yet remains unclear. [source] Homeostatic role of IL-7 in HIV-1 infected children on HAART: Association with immunological and virological parametersACTA PAEDIATRICA, Issue 2 2005S Resino Abstract Aim: To investigate the role of IL-7 in HIV-infected children on highly active antiretroviral therapy (HAART) and its association with laboratory parameters related to disease progression. Patients and methods: A cross-sectional study in 31 vertically HIV-infected children (median age 8.4 y) treated with HAART, and a longitudinal study in four of those same children was carried out. In both studies, viral load, CD4+ T-cell counts, thymic production of T cells by TCR rearrangement excision circles (TRECs), IL-7 plasma levels and viral phenotype were determined. Results: IL-7 levels were higher in HIV-infected children than in age-matched, uninfected controls. In addition, HIV children with CD4+ T cells between 200 and 500 T cells/mm3 had higher IL-7 levels and lower TREC values than HIV-infected children with CD4+ T cells >500 T cells/mm3. IL-7 levels were higher in children with syncytium-inducing (SI) phenotype than in those with non-syncytium-inducing (NSI) variants. During the follow-up of four HIV children, the decrease in viral load after HAART was always associated with a recovery of CD4+ T cells and TRECs, which was followed by a decrease in IL-7 returning to the levels present prior to the drop in CD4+ T cells. The four HIV-infected children had SI/X4 isolates in PBMC before HAART, and the viral phenotype switched to NSI/R5 after HAART. Conclusion: Our data suggest that IL-7 plays a key role in the maintenance of T-cell homeostasis in HIV-infected children on HAART, both through peripheral expansion and through a thymus-dependent mechanism. [source] | ||||||||||