T-cell dynamics during acute SIV infection.

Abstract

To delineate T-cell dynamics during acute SIV infection, particularly of phenotypically defined memory T cell subsets. T cells are a heterogeneous mix of naive and memory subsets delineated by simultaneously measuring CD4, CD8, CD45RA/RO, CD11a, CD28, and CD27. The effects of SIV infection on these subsets was measured to evaluate the impact of changes in functionally distinct cell types during pathogenesis. Peripheral blood was obtained from six SIV-infected macaques at multiple times before and after SIV infection and analyzed using 12-color flow cytometry. Acute infection was characterized by an initial lymphopenia caused by a decline in B cells. Total T-cell counts remained steady during the early acute phase; however, CD4 cell counts declined while CD8 T cells increased. The decline in CD4 T cells was a result of a decline in both naive and memory cells. CCR5+ or CD103+ subsets of CD4 T cells were depleted but only partially accounted for the decline of CD4 memory T cells, suggesting that acute infection was associated with a rapid redistribution of T cells from the periphery. Naive CD8 cell counts declined while memory CD8 cell counts increased. The increase coincided with declines in plasma viremia and was made up initially of CD27-CD28- (effector) cells; subsequently, the predominant phenotype became CD27+CD28-, akin to central memory cells. A complete understanding of the T-cell dynamics during acute SIV or HIV infection requires the simultaneous evaluation of a broad spectrum of T-cell subsets. Changes in homeostasis and associated immunopathogenesis can no longer be accurately described simply by measuring naive and memory T-cell subsets.