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. SUBPROJECT DESCRIPTION: Dysfunctional CD8 T cells are frequently found in uncontrolled chronic infections, including HIV. In mice and humans, PD-1, an inhibitory receptor of the CD28 family, has been identified to be upregulated on CD8-positive and CD4-positive T cells and to interfere with the proliferation and function of these cells. However, little is known about the role of PD-1 in SIV-infected rhesus macaques. We investigated the expression of PD-1 on CD8-positive and CD4-positive T cells in acutely and chronically SIV-infected rhesus macaques with varying ability to control viral replication. In normal controls, PD-1 was expressed at relatively low levels on na?ve CD4-positive and CD8-positive T cells, but was found at a significantly higher degree on central memory and effector memory T lymphocytes. In SIV-infected animals, PD-1 was significantly upregulated on central memory CD8-positive and CD4-positive T cells, as compared with normal controls. Analysis of PD-1 expression on SIV-specific CD8-positive T cells revealed higher levels of PD-1 expression on cells specific for the relatively conserved Mamu A*01-restricted Gag CM9 epitope than on cells specific for epitopes prone to escape, suggesting that ongoing antigenic stimulation is necessary for upregulation of PD-1 expression. However, we did not observe a correlation between viral load and PD-1 expression on SIV-specific CD8-positive T cells. Our findings provide insights into the expression of PD-1 on subsets of memory T cells in SIV-infected macaques and suggest that the SIV-macaque model may prove useful for efforts to examine the effects of modulation of PD-1/PDL-1 interactions on control of SIV/HIV infection.
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