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

J Exp Med. 2004 Sep 20;200(6):749-59. doi: 10.1084/jem.20040874. Epub 2004 Sep 13.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • Collagen / metabolism
  • Digestive System / immunology*
  • Digestive System / virology
  • HIV Infections / etiology
  • HIV Infections / immunology*
  • Humans
  • Immunologic Memory
  • Lymph Nodes / immunology
  • Lymphocyte Activation
  • Receptors, CCR5 / analysis


  • Receptors, CCR5
  • Collagen