Enhancement of CD8+ T cell responses by ICOS/B7h costimulation.
Although the recently identified ICOS/B7h costimulatory counterreceptors are critical regulators of CD4(+) T cell responses, their ability to regulate CD8(+) responses is unclear. Here we report using a tumor-rejection model that ectopic B7h expression can costimulate rejection by CD8(+) T cells in the absence of CD4(+) T cells. Although responses of naive T cells were significantly augmented by priming with B7h, B7h was surprisingly effective in mobilizing recall responses of adoptively transferred T cells. To explore why secondary responses of CD8(+) T cells were particularly enhanced by B7h, kinetics of ICOS up-regulation, proliferative responses, and cytokine production were compared from both naive and rechallenged 2C-transgenic T cells costimulated in vitro. Although B7h costimulated proliferative responses from both CD8(+) populations, rechallenged cells were preferentially costimulated for IL-2 and IFN-gamma production. These results indicate that ICOS/B7h counterreceptors likely function in vivo to enhance secondary responses by CD8(+) T cells.
Wallin
J J
JJ
Immunology Division, Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Liang
L
L
Bakardjiev
A
A
Sha
W C
WC
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D011506:Proteins / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C556692:ICOS protein, human; C498514:ICOSLG protein, human; C556694:Icos protein, mouse; C400230:Icosl protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D011506:Proteins