Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 121, Issue 3, Pages 998-1008Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI45157
Keywords
-
Categories
Funding
- NIH [AI028246, AI048484, AI056997]
- Yerkes base grant [P51-00165]
- National Cancer Institute, NIH [HHSN261200800001E]
Ask authors/readers for more resources
The hallmark of HIV-1 and SW infections is CD4(+) T cell depletion. Both direct cell killing and indirect mechanisms related to immune activation have been suggested to cause the depletion of T cells. We have now identified a mechanism by which immune activation-induced fibrosis of lymphoid tissues leads to depletion of naive T cells in HIV-1 infected patients and SW-infected rhesus macaques. The T regulatory cell response to immune activation increased procollagen production and subsequent deposition as fibrils via the TGF-beta 1 signaling pathway and chitinase 3-like-1 activity in fibroblasts in lymphoid tissues from patients infected with HIV-1. Collagen deposition restricted T cell access to the survival factor IL-7 on the fibroblastic reticular cell (FRC) network, resulting in apoptosis and depletion of T cells, which, in turn, removed a major source of lymphotoxin-beta, a survival factor for FRCs during SW infection in rhesus macaques. The resulting loss of FRCs and the loss of IL-7 produced by FRCs may thus perpetuate a vicious cycle of depletion of T cells and the FRC network. Because this process is cumulative, early treatment and antifibrotic therapies may offer approaches to moderate T cell depletion and improve immune reconstitution during HIV-1 infection.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available