Collagen deposition in HIV-1 infected lymphatic tissues and T cell homeostasis.
Schacker, Timothy W. 1; Nguyen, Phuong L. 2; Beilman, Gregory J. 3; Wolinsky, Steven 4; Larson, Matthew 1; Reilly, Cavan 5; Haase, Ashley T. 6
[Article] Journal of Clinical Investigation. 110(8):1133-1139, October 2002.

(Format: HTML, PDF)

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.

Copyright (C) 2002 The American Society for Clinical Investigation, Inc.