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

Timothy W. Schacker, Phuong L. Nguyen, Gregory J. Beilman, Steven Wolinsky, Matthew Larson, Cavan Reilly, Ashley T. Haase

Research output: Contribution to journalArticle

193 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1133-1139
Number of pages7
JournalJournal of Clinical Investigation
Volume110
Issue number8
DOIs
StatePublished - Oct 2002

ASJC Scopus subject areas

  • Medicine(all)

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    Schacker, T. W., Nguyen, P. L., Beilman, G. J., Wolinsky, S., Larson, M., Reilly, C., & Haase, A. T. (2002). Collagen deposition in HIV-1 infected lymphatic tissues and T cell homeostasis. Journal of Clinical Investigation, 110(8), 1133-1139. https://doi.org/10.1172/JCI0216413