Identifying the target cell in primary simian immunodeficiency virus (SIV)infection: Highly activated memory CD4+ T cells are rapidly eliminated in early SIV infection in vivo

It has recently been shown that rapid and profound CD4(+) T-cell depletion occurs almost exclusively within the intestinal tract of simian immunodefic iency virus (SIV)-infected macaques within days of infection. Here we demon strate (by three- and four-color flow cytometry) that this depletion is spe cific to a definable subset of CD4(+) T cells, namely, those having both a highly and/or acutely activated (CD69(+) CD38(+) HLA-DR+) and memory (CD45R A(-) Leu8(-)) phenotype. Moreover, we demonstrate that this subset of helpe r T cells is found primarily within the intestinal lamina propria, Viral tr opism for this particular cell type (which has been previously suggested by various studies in vitro) could explain why profound CD4(+) T-cell depleti on occurs in the intestine and not in peripheral lymphoid tissues in early SIV infection. Furthermore, we demonstrate that an acute loss of this speci fic subset of activated memory CD4(+) T cells may also be detected in perip heral blood and lymph nodes in early SIV infection. However, since this par ticular cell type is present in such small numbers in circulation, its loss does not significantly affect total CD4(+) T cell counts, This finding sug gests that SIV and, presumably, human immunodeficiency virus specifically i nfect, replicate in, and eliminate definable subsets of CD4(+) T cells in v ivo.