NDLI: Trafficking of Human Immunodeficiency Virus Type 1-Specific CD8+ T Cells to Gut-Associated Lymphoid Tissue during Chronic Infection

Content Provider	PubMed Central
Author	Shacklett, Barbara L. Cox, Catherine A. Sandberg, Johan K. Stollman, Neil H. Jacobson, Mark A. Nixon, Douglas F.
Copyright Year	2003
Abstract	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 αΕβ7 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 αΕβ7 integrin, but CD4+/CD8+ T-cell ratios in blood and GALT were similar. The percentage of GALT CD8+ T cells expressing αΕβ7 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.
Related Links	http://dx.doi.org/10.1128/jvi.77.10.5621-5631.2003
Ending Page	5631
Page Count	11
Starting Page	5621
File Format	PDF
ISSN	0022538X
e-ISSN	10985514
Journal	Journal of Virology
Issue Number	10
Volume Number	77
Language	English
Publisher	American Society for Microbiology
Publisher Date	2003-05-15
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Immunology Virology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Virology Immunology Microbiology Insect Science

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