Cycling of gut mucosal CD4+ T cells decreases after prolonged anti-retroviral therapy and is associated with plasma LPS levels.
The gut mucosa is an important site of HIV immunopathogenesis with severe depletion of CD4+ T cells occurring during acute infection. The effect of prolonged anti-retroviral therapy (ART) on cycling and restoration of T lymphocytes in the gut remains unclear. Colon and terminal ileal biopsies and peripheral blood samples were collected from viremic, untreated, HIV-infected participants, patients treated with prolonged ART (>5 years), and uninfected controls and analyzed by flow cytometry. In the gut, the proportion of cycling T cells decreased and the number of CD4+ T cells normalized in treated patients in parallel with beta 7 expression on CD4+ T cells in blood. Cycling of gut T cells in viremic patients was associated with increased plasma LPS levels, but not colonic HIV-RNA. These data suggest that gut T-cell activation and microbial translocation may be interconnected whereas prolonged ART may decrease activation and restore gut CD4+ T cells.
Ciccone
E J
EJ
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
Read
S W
SW
Mannon
P J
PJ
Yao
M D
MD
Hodge
J N
JN
Dewar
R
R
Chairez
C L
CL
Proschan
M A
MA
Kovacs
J A
JA
Sereti
I
I
D000328:Adult; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002453:Cell Cycle / Q000276:immunology; D003106:Colon / Q000276:immunology; D015536:Down-Regulation; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007082:Ileum / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D008070:Lipopolysaccharides / Q000097:blood*; D008875:Middle Aged; D013997:Time Factors
D044966:Anti-Retroviral Agents; D008070:Lipopolysaccharides