title: Collagen deposition in HIV-1 infected lymphatic tissues and T cell homeostasis.
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.
authors.affiliation: Department of Medicine/Infectious Diseases, University of Minnesota, MMC 250, 516 Delaware Street, Minneapolis, Minnesota 55455, USA. schacker@lenti.med.umn.edu
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Schacker
authors.forename: Phuong L
authors.initials: PL
authors.lastname: Nguyen
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Beilman
authors.forename: Steven
authors.initials: S
authors.lastname: Wolinsky
authors.forename: Matthew
authors.initials: M
authors.lastname: Larson
authors.forename: Cavan
authors.initials: C
authors.lastname: Reilly
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Haase
mesh_terms: 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
chemical_list: D003094:Collagen