title: Superantigen responses and co-stimulation: CD28 and CTLA-4 have opposing effects on T cell expansion in vitro and in vivo.
abstract: Co-stimulation via the CD28/CTLA-4 system appears critical for T cell proliferation to peptide antigens presented in association with MHC. In this study, we examine the roles of CD28 and CTLA-4 in the response of murine T cells to the superantigen staphylococcal enterotoxin B (SEB). In vitro, antibodies against B7-1/B7-2 or Fab fragments of anti-CD28 antibodies significantly inhibit the response of splenocytes to SEB. Conversely, Fab fragments of anti-CTLA-4 antibodies augment the proliferative response. Further, addition of blocking antibodies directed against B7-1/B7-2 augment proliferation co-stimulated by intact anti-CD28 antibodies. These data support the hypothesis that CD28 and CTLA-4 exert opposing effects upon early T cell activation. In vivo, intact anti-CD28 antibodies and non-stimulatory Fab fragments of anti-CD28 appear to have similar inhibitory effects upon the expansion of V beta 8+ T cells. In contrast, both intact and Fab fragments of anti-CTLA-4 appear to amplify this expansion. We conclude that the SEB response is significantly augmented by CD28-derived signaling and this in turn may be attenuated by signals through CTLA-4.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Krummel
authors.forename: T J
authors.initials: TJ
authors.lastname: Sullivan
authors.forename: J P
authors.initials: JP
authors.lastname: Allison
mesh_terms: D000069594:Abatacept; D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D017951:Antigen Presentation; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology*; D060908:CTLA-4 Antigen; D002455:Cell Division; D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology*
chemical_list: D019138:Antibodies, Blocking; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D004768:Enterotoxins; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D018089:Superantigens; D000069594:Abatacept