Collagen deposition in HIV-1 infected lymphatic tissues and T cell homeostasis.
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.
Schacker
Timothy W
TW
Department of Medicine/Infectious Diseases, University of Minnesota, MMC 250, 516 Delaware Street, Minneapolis, Minnesota 55455, USA. schacker@lenti.med.umn.edu
Nguyen
Phuong L
PL
Beilman
Gregory J
GJ
Wolinsky
Steven
S
Larson
Matthew
M
Reilly
Cavan
C
Haase
Ashley T
AT
D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003094:Collagen / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D015497:HIV-1; D006706:Homeostasis; D006801:Humans; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D011446:Prospective Studies
D003094:Collagen