HIV antigens can induce TGF-beta(1)-producing immunoregulatory CD8+ T cells.
HIV-infected individuals may progressively lose both HIV-specific and unrelated CTL responses despite the high number of circulating CD8+ T cells. In this study, we report that approximately 25% of HIV+ donors produced TGF-beta(1) in response to stimulation with HIV proteins or peptides. The production of TGF-beta(1) was sufficient to significantly reduce the IFN-gamma response of CD8+ cells to both HIV and vaccinia virus proteins. Ab to TGF-beta reversed the suppression. We found the source of the TGF-beta(1) to be predominantly CD8+ cells. Different peptide pools stimulated TGF-beta(1) and IFN-gamma in the same individual. The TGF-beta(1) secreting cells have distinct peptide specificity from the IFN-gamma producing cells. This represents an important mechanism by which an HIV-specific response can nonspecifically suppress both HIV-specific and unrelated immune responses.
Garba
Mohammed L
ML
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill NC 27599, USA.
Pilcher
Christopher D
CD
Bingham
Andrea L
AL
Eron
Joseph
J
Frelinger
Jeffrey A
JA
D000328:Adult; D000906:Antibodies / Q000494:pharmacology; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D005260:Female; D005822:Genetic Vectors; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D011994:Recombinant Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D053773:Transforming Growth Factor beta1; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D000906:Antibodies; D015488:HIV Antigens; D010455:Peptides; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma