Trafficking of human immunodeficiency virus type 1-specific CD8+ T cells to gut-associated lymphoid tissue during chronic infection

J Virol. 2003 May;77(10):5621-31. doi: 10.1128/jvi.77.10.5621-5631.2003.


Gut-associated lymphoid tissue (GALT) is a significant but understudied lymphoid organ, harboring a majority of the body's total lymphocyte population. GALT is also an important portal of entry for human immunodeficiency virus (HIV), a major site of viral replication and CD4(+) T-cell depletion, and a frequent site of AIDS-related opportunistic infections and neoplasms. However, little is known about HIV-specific cell-mediated immune responses in GALT. Using lymphocytes isolated from rectal biopsies, we have determined the frequency and phenotype of HIV-specific CD8(+) T cells in human GALT. GALT CD8(+) T cells were predominantly CD45RO(+) and expressed CXCR4 and CCR5. In 10 clinically stable, chronically infected individuals, the frequency of HIV Gag (SL9)-specific CD8(+) T cells was increased in GALT relative to peripheral blood mononuclear cells by up to 4.6-fold, while that of cytomegalovirus (CMV)-specific CD8(+) T cells was significantly reduced (P = 0.012). Both HIV- and CMV-specific CD8(+) T cells in GALT expressed CCR5, but only HIV-specific CD8(+) T cells expressed alpha E beta 7 integrin, suggesting that mucosal priming may account for their retention in GALT. Chronically infected individuals exhibited striking depletion of GALT CD4(+) T cells expressing CXCR4, CCR5, and alpha E beta 7 integrin, but CD4(+)/CD8(+) T-cell ratios in blood and GALT were similar. The percentage of GALT CD8(+) T cells expressing alpha E beta 7 was significantly decreased in infected individuals, suggesting that HIV infection may perturb lymphocyte retention in GALT. These studies demonstrate the feasibility of using tetramers to assess HIV-specific T cells in GALT and reveal that GALT is the site of an active CD8(+) T-cell response during chronic infection.

Publication types

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

MeSH terms

  • Adult
  • CD4-CD8 Ratio
  • CD8-Positive T-Lymphocytes / immunology*
  • Chronic Disease
  • Cytomegalovirus / immunology
  • Cytotoxicity, Immunologic
  • Female
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Immunophenotyping
  • Lymphocyte Activation*
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / immunology*
  • Male
  • Middle Aged
  • Mucous Membrane / immunology
  • Rectum / immunology*