This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have been examining neonatal macaques and tissues to determine why SIV/HIV progresses faster in neonates compared to adults. One limitation in Immunologic research in nonhuman primates is occasionally limited by the availability of reagents that cross-react in nonhuman primates. One major limitation has been the lack of a monoclonal antibody to CD45RO. One current study o this project examined the reactivity and specificity of another antibody against CD45RO, clone OPD4, in macaques. Here we demonstrate that OPD4 specifically labels memory CD4+ T cells in approximately 44% of rhesus macaques (Macaca mulatta) of Indian but not Chinese origin. In contrast, tissues from pigtail macaques (Macaca nemestrina) react with this clone, indicating that OPD4 may be useful for examining memory CD4+ T cells in certain macaques, but its utility may be limited in other species or even among individual macaques. In another project we have been examining double positive CD4(+)CD8(+) (DP) T cells in neonates. Here we demonstrate the functional and immunophenotypic characteristics of DP cells in 6 different tissues from normal neonatal rhesus macaques (Macaca mulatta) between 0-21 days of age. In general, intestinal DP T cells of neonates have higher percentages of memory markers (CD28(+)CD95(+)CD45RA(low)CD62L(low)) and proliferation compared to SP CD4(+) and CD8(+) T cells. In addition, percentages of DP T cell increase and CD62L expression decreases as animals mature suggesting that DP cells mature and proliferate with maturity and/or antigen exposure. Consistent with this, intestinal DP T cells in neonates express higher levels of CCR5 and are the primary targets in SIV infection. Collectively, these findings demonstrate that intestinal DP T cells of neonates are proliferating, activated, memory cells and are likely involved in regulating immune responses, in contrast to immature DP T cells in the thymus.
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