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 journalArticlepeer-review

202 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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