This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Natural killer cells (NK) provide the first line of defense following encounters with different virus-infected cells. Alteration of NK cell numbers, phenotype and function was reported in HIV-1 infected humans soon after seroconversion.
Aims. 1) To test the cross-reactivity of different Ab clones in identifying NK cells in African green monkeys (AGMs), and then to compare the numbers of NK cells in blood and tissues along with their phenotypes between NHP species progressing to AIDS (pig-tailed macaques [PTMs]) and non-progressive hosts (AGMs). 2) To determine changes in the phenotype of NK cells after SIVagm infection in AGMs and PTMs; 3) To determine the dynamics of different NK cell subsets in SIVagm-infected AGMs and PTMs.Results. As reported for rhesus (RMs) and PTMs, CD56 is not an appropriate marker to identify NK cells in AGMs. CD16 is a reliable marker for identification of NK cells in normal AGMs despite its cross-reactivity with a small population of monocytes (1-5%). Association of NKG2A and CD16 can identify the majority of NK cells in normal AGMs, as described in RMs and PTMs. NKp30 and NKp46 identified smaller NK populations in AGMs and PTMs. Our study does not confirm previous data about absence of NKp30 expression in African NHPs. AGMs have approx. 65% NKp30+CD3neg lymphocytes. Only a few NK cells were found in lymph nodes and intestine in AGMs and PTMs. Dynamics of different NK cell populations during SIVagm infection revealed differences between pathogenic and non-pathogenic models. In AGMs, neither CD8+CD3negCD20neg or CD16+CD3neg populations showed significant variation during the SIVagm infection. In PTMs, these NK cell subpopulations showed rapid depletion very early (day 2) post SIV inoculation and a significant decrease during chronic infection. Our study identified the appropriate markers for the study of NK cells in AGMs. The lack of NKp30 expression is not a general rule for the African natural hosts of SIV and therefore it is unlikely to play a major role preventing disease progression in these species. The differences observed in the dynamics of different NK cell subpopulations between pathogenic and non-pathogenic models further confirms that differences in innate immunity is one of the key feature driving the non-pathogenicity of SIV infection in natural hosts.
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