Regulation and role of IL-7 production in HIV-1 infection

摘要: The concentration of interleukin-7 (IL-7) in human serum is elevated various clinical conditions associated with lymphopenia, including HIV-1 infection. IL-7 an essential factor for T cell differentiation and survival, it was suggested that high may represent a homeostatic response to depletion, which promote regeneration. In order increase our understanding on the regulation production, we investigated specimens from infected patients during chronic infection long term non-progressors (LTNPs). Serum levels correlated T-cell depletion individuals. some patients, observed decreased upon progression AIDS, suggesting role maintenance sporadic cases. Interestingly, were significantly lower stable LTNPs than who lost LTNP status 3-year follow-up (P<0.001), indicating might be valuable marker status. number CD8+CD28T cells increases aging These have reduced expression receptor alpha (IL-7R), as compared CD8+CD28+ cells. As been dendritic suppression, analyzed whether numbers could lead impaired responses. Peripheral blood both HIV-infected non-infected individuals promoted activation. accumulation thus contribute inflammatory reactions immune Stromal intestinal epithelial are known produce IL-7. mechanisms cellular factors regulating production still unclear. We assessed IL-1 IFN-, cytokines produced conditions, impact production. used (DLD-1 line) bone marrow stromal (HS27 evaluate at mRNA protein levels. To assess treatment HS27 and/or IFN- leads changes gene cytokines, Toll-like receptors (TLRs) chemokines, analysed profiles using whole-genome microarray Human Gene 1.0 ST. found enhanced (P<0.001) lines. led significant down-regulation revealed dramatic their receptors, IFN regulatory (IRF-1 2) important chemo-attractants results verified by additional methods. Our discussed setting inflammation survival gut compartment where homeostasis homing It previously reported stimulate activation CD95 mediated apoptosis. B abnormalities increased apoptosis via death pathway loss memory Here present novel mechanism can presence concentration. cultured induced resting together sensitivity mediator molecule responsible priming identified cytokine secreted IFN-γ correlation level circulating lymphocytes non-viremic indicate potential link between conclusion presented this PhD thesis highlight dependent exposure producing cytokines. also data through cells; finding outcome therapy will ongoing studies. ISBN 978-91-7457-338-1