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T-cell dynamics during acute SIV infection

Mattapallil, Joseph Ja; Letvin, Norman Lb; Roederer, Marioa

Basic Science

Objectives: To delineate T-cell dynamics during acute SIV infection, particularly of phenotypically defined memory T cell subsets.

Design: 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.

Methods: Peripheral blood was obtained from six SIV-infected macaques at multiple times before and after SIV infection and analyzed using 12-color flow cytometry.

Results: 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.

Conclusions: 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.

From the aVaccine Research Center, NIAID, NIH, Bethesda, Maryland and the bBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

Requests for reprints to: M. Roederer, Room 5509, 40 Convent Dr, Bethesda, MD 20895, USA.

Received: 6 February 2003; revised: 17 April 2003; accepted: 7 May 2003.

© 2004 Lippincott Williams & Wilkins, Inc.