Differential production of IL-10 by T cells and monocytes of HIV-infected individuals: association of IL-10 production with CD28-mediated immune responsiveness.
Immune unresponsiveness in HIV-1 infection can result from impaired signals delivered by the costimulatory CD28-B7 pathway and the altered production of immunoregulatory cytokines, in particular IL-10, whose production is altered in HIV-1 infection. In this study we investigate IL-10 regulation in T cells and monocytes from HIV+ individuals, and its association with CD28-mediated T cell proliferation. IL-10 production as analysed in T cell- and monocyte-depleted peripheral blood mononuclear cells (PBMC), and by intracellular staining at the single-cell level, reveals a defect in IL-10 production by CD4+ and CD8+ T cells, whereas monocytes constitute the major IL-10-producing cell type. To investigate the impact of IL-10 on immune responsiveness, CD28-mediated proliferative responses in HIV+ individuals were correlated with PHA-induced IL-10 production. CD4+ T cells expressed CD28, yet exhibited markedly reduced CD28-mediated cell proliferation. This CD28-mediated CD4+ T cell proliferation was found to be inversely associated with the levels of PHA-induced IL-10 production and could be restored, at least in part, by anti-IL-10 antibodies. These results suggest that IL-10 production is differentially regulated in T cells and monocytes of HIV+ individuals, and that IL-10 may have a role in inducing immune unresponsiveness by modulating the CD28-B7 pathway.
Division of Virology and Molecular Immunology, Research Institute, Children's Hospital of Eastern Ontario, University of Ottawa, Canada.
A
A
Kumar
J B
JB
Angel
M P
MP
Daftarian
K
K
Parato
W D
WD
Cameron
L
L
Filion
F
F
Diaz-Mitoma
D000328:Adult; D018106:CD28 Antigens / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D015536:Down-Regulation; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008934:Mitogens / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism*
D018106:CD28 Antigens; D008934:Mitogens; D010835:Phytohemagglutinins; D016753:Interleukin-10