Description): Neonates are more susceptible than adults to infectious diseases, particularly those of viral origin. The increased susceptibility to viral infections is particularly evident in HIV children infected who have a rapid disease course and increased viral loads compared to adults. While this is well known, explanations for the increased susceptibility of children are largely speculative and involve the concept of """"""""immunologic immaturity"""""""". While this phrase is widely used, it is poorly defined. The objective of this proposal is to carefully define developmental changes in the immunophenotypic composition and function of the systemic and mucosal immune system from neonate to adult in normal and simian immunodeficiency virus (SIV)-infected macaques. In this model, SIV serves as a useful tool to determine which differences between the immature and mature immune system are responsible for the increased susceptibility to SIV. The hypothesis is that the normal neonatal immune system is compartmentalized and that, while the systemic immune system may be functionally immature, the mucosal immune system is competent at birth, containing large numbers of activated, memory T cells that serve as targets for HIV infection. Furthermore, the investigators hypothesize that these cells are geared toward the production of type 2 cytokines, which diminish the neonates capacity to generate an effective cell-mediated immune response. Finally, they hypothesize that neonatal tissues have increased expression of relevant chemokine receptors that function as cofactors for HIV infection, compared to adult tissues. To evaluate these hypotheses, the investigator will examine normal (uninfected) and SIV-infected rhesus macaques, from neonate to adult to: 1) Characterize the ontogeny of T cell development, cytokine production, and the sequential expression and development of chemokine receptors in mucosal and peripheral lymphoid tissues of neonatal macaques at various stages of development, and to compare them to those of juvenile and adult macaques and; 2) Determine the effects of SIV infection on lymphocyte immunophenotype, cytokine production and chemokine receptor expression in neonatal macaques by examining sequential changes in mucosal and peripheral lymphoid tissues at various time points after infection with both pathogenic and nonpathogenic clones of SIV. The data will be compared to data already obtained from juvenile and adult macaques infected with equal doses of the same viral stocks.
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