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J Exp Med. 2004 Sep 20;200(6):749-59. Epub 2004 Sep 13.

CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract.

Author information

  • 1Human Immunology Section, Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Dr., Room 3509, Bethesda, MD 20892, USA.

Abstract

The mechanisms underlying CD4(+) T cell depletion in human immunodeficiency virus (HIV) infection are not well understood. Comparative studies of lymphoid tissues, where the vast majority of T cells reside, and peripheral blood can potentially illuminate the pathogenesis of HIV-associated disease. Here, we studied the effect of HIV infection on the activation and depletion of defined subsets of CD4(+) and CD8(+) T cells in the blood, gastrointestinal (GI) tract, and lymph node (LN). We also measured HIV-specific T cell frequencies in LNs and blood, and LN collagen deposition to define architectural changes associated with chronic inflammation. The major findings to emerge are the following: the GI tract has the most substantial CD4(+) T cell depletion at all stages of HIV disease; this depletion occurs preferentially within CCR5(+) CD4(+) T cells; HIV-associated immune activation results in abnormal accumulation of effector-type T cells within LNs; HIV-specific T cells in LNs do not account for all effector T cells; and T cell activation in LNs is associated with abnormal collagen deposition. Taken together, these findings define the nature and extent of CD4(+) T cell depletion in lymphoid tissue and point to mechanisms of profound depletion of specific T cell subsets related to elimination of CCR5(+) CD4(+) T cell targets and disruption of T cell homeostasis that accompanies chronic immune activation.

PMID:
15365096
[PubMed - indexed for MEDLINE]
PMCID:
PMC2211962
Free PMC Article

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