Depletion of regulatory T cells in HIV infection is associated with immune activation.
Immune activation during chronic HIV infection is a strong clinical predictor of death and may mediate CD4(+) T cell depletion. Regulatory T cells (Tregs) are CD4(+)CD25(bright)CD62L(high) cells that actively down-regulate immune responses. We asked whether loss of Tregs during HIV infection mediates immune activation in a cross-sectional study of 81 HIV-positive Ugandan volunteers. We found that Treg number is strongly correlated with both CD4(+) and CD8(+) T cell activation. In multivariate modeling, this relationship between Treg depletion and CD4(+) T cell activation was stronger than any other clinical factor examined, including viral load and absolute CD4 count. Tregs appear to decline at different rates compared with other CD4(+) T cells, resulting in an increased regulator to helper ratio in many patients with advanced disease. We hypothesize that this skewing may contribute to T cell effector dysfunction. Our findings suggest Tregs are a major contributor to the immune activation observed during chronic HIV infection.
Eggena
Mark P
MP
Division of Infectious Diseases, University of California, San Francisco, CA 94143, USA.
Barugahare
Banson
B
Jones
Norman
N
Okello
Martin
M
Mutalya
Steven
S
Kityo
Cissy
C
Mugyenyi
Peter
P
Cao
Huyen
H
D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D019041:L-Selectin; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015375:Receptors, Interleukin-2; D014454:Uganda
D015375:Receptors, Interleukin-2; D019041:L-Selectin