Regulatory T cells suppress CD8+ T cell responses induced by direct priming and cross-priming and moderate immunodominance disparities.
Little is known regarding the participation of CD4+ CD25+ regulatory T cells (Treg) in TCD8+ responses. In this study, we show that Treg depletion via treatment with anti-CD25 mAb (PC61) significantly enhances TCD8+ responses to influenza A virus, vaccinia virus, and SV40-transformed cells induced by either direct priming or cross-priming. PC61 did not enhance TCD8+ responses in CD4-deficient mice, providing the initial demonstration that PC61 acts on a subset of TCD4+, and not on other cells that express either CD25 or a fortuitously cross-reactive Ag. We further show that Treg selectively suppress responses to the most immunodominant TCD8+ determinants in the three systems examined. Therefore, Treg influence TCD8 immunodominance hierarchies by moderating disparities in responses to different determinants.
Haeryfar
S M Mansour
SM
Laboratory of Viral Diseases, National Institute of Allergies and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
DiPaolo
Richard J
RJ
Tscharke
David C
DC
Bennink
Jack R
JR
Yewdell
Jonathan W
JW
D000595:Amino Acid Sequence; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D000956:Antigens, Viral / Q000235:genetics; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D007108:Immune Tolerance; D016056:Immunodominant Epitopes / Q000235:genetics; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D000952:Antigens, Polyomavirus Transforming; D000956:Antigens, Viral; D015704:CD4 Antigens; D016056:Immunodominant Epitopes; D010446:Peptide Fragments