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J Clin Invest. 2002 Oct;110(8):1133-9.

Collagen deposition in HIV-1 infected lymphatic tissues and T cell homeostasis.

Author information

1
Department of Medicine/Infectious Diseases, University of Minnesota, MMC 250, 516 Delaware Street, Minneapolis, Minnesota 55455, USA. schacker@lenti.med.umn.edu

Abstract

Lymphatic tissues (LTs) are structurally organized to promote interaction between antigens, chemokines, growth factors, and lymphocytes to generate an immunologic response and maintain normal-sized populations of CD4(+) and CD8(+) T cells. Inflammation and tissue remodeling that accompany local innate and adaptive immune responses to HIV-1 replication cause damage to the LT architecture. As a result, normal populations of CD4(+) and CD8(+) T cells cannot be supported and antigen-lymphocyte interactions are impaired. This conclusion is supported herein following LT sampling before and during anti-HIV therapy in persons with acute, chronic, and late-stage HIV-1 infection. Among seven individuals treated with anti-retroviral therapy (ART) and four individuals deferring therapy we found evidence of significant paracortical T cell zone damage associated with deposition of collagen, the extent of which was inversely correlated with both the size of the LT CD4(+) T cell population and the change in peripheral CD4(+) T cell count with anti-HIV therapy. The HIV-1-associated inflammatory changes and scarring in LT both limit the ability of the tissue to support and reestablish normal-sized populations of CD4(+) T cells and suggest a novel mechanism of T cell depletion that may explain the failure of ART to significantly increase CD4(+) T cell populations in some HIV-1-infected persons.

PMID:
12393849
PMCID:
PMC150803
DOI:
10.1172/JCI16413
[Indexed for MEDLINE]
Free PMC Article

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