CD152 ligation by CD80 on T cells is required for the induction of unresponsiveness by costimulation-deficient antigen presentation.
Two apparently contradictory observations have been made concerning peripheral T cell tolerance; costimulation-deficient Ag presentation leads to unresponsiveness, and CTLA4 (CD152) ligation is required for unresponsiveness to be induced. This issue was addressed using a CD80- CD86low B cell line to present Ag to DO.11.10 naive CD4+ T cells. Proliferation was substantially enhanced by anti-CD80 or anti-CD152, but was inhibited by anti-CD86. Furthermore, anti-CD80 partially, and anti-CD152 totally protected cloned DO.11.10 T cells from the induction of unresponsiveness following culture with peptide and Chinese hamster ovary H2-Ad+ CD80- CD86- cells. Fab of anti-CD80 caused similar enhancement, and coimmobilized anti-CD80 failed to costimulate the anti-CD3 response of purified T cells, indicating that direct signaling by anti-CD80 was not responsible for these effects. The possibility that anti-CD80 liberated CD28 molecules that were sequestered by the T cell-expressed CD80, enabling them to coaggregate with TCR:CD3 complexes was excluded by finding that anti-CD80 and anti-CD152 individually caused maximal enhancement, rather than having additive effects. These data suggest that T cell-expressed CD80 has a regulatory function and plays a key role in the induction of unresponsiveness due to costimulation-deficient Ag presentation by the ligation of CD152 on neighboring, or even the same, T cell.
Chai
J G
JG
Department of Immunology, Imperial College School of Medicine, and Transplantation Biology Group, Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom.
Vendetti
S
S
Amofah
E
E
Dyson
J
J
Lechler
R
R
D000069594:Abatacept; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen; D002460:Cell Line; D017635:Clonal Anergy / Q000235:genetics / Q000276:immunology; D006224:Cricetinae; D007108:Immune Tolerance / Q000276:immunology*; D018796:Immunoconjugates; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D000069594:Abatacept