We have continued to examine the mucosal immunopathogenesis of SIV infection in the intestinal mucosa in order to determine why selective and profound CD4+ T cell depletion occurs specifically within mucosal tissues in early SIV infection To accomplish this, we have broadened our studies to extensively characterize the immunophenotype of the CD4+ T cells that are targeted in early SIV infection by four-color flow cytometry By examining uninfected normal rhesus macaques, we have shown that intestinal CD4+ T cells consist of a homogenous population of activated (CD69+CD38+HLA-DR+), memory (CD45RA-, L-selectin-), CD2+CD3+CD4+ T cells Since in vitro studies of both HIV and SIV have demonstrated that optimal viral replication occurs specifically within activated, memory CD4+ T cells, we hypothesized that the reason the intestinal cells are rapidly eliminated was that they are essentially all activated, memory cells To test this hypothesis, we followed acutely i nfec ted animals by four-color immunophenotyping of peripheral blood lymphocytes to determine whether a loss of this subset could be detected in other tissues Although activated, memory CD4+ T cells represent only a small proportion of peripheral blood lymphocytes, we could consistently find an early loss of this particular subset of CD4+ T cells could also be detected in the blood in relatively the same time frame as the intestinal CD4+ T cell depletion Combined, our data indicate that activated memory CD4+ T cells are the initial target for viral infection and amplification Future studies will explore the mechanisms by which these cells are depleted (apoptosis versus direct cell lysis, etc )
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