Evidence that induction of tolerance in vivo involves active signaling via a B7 ligand-dependent mechanism: CTLA4-Ig protects V beta 8+ T cells from tolerance induction by the superantigen staphylococcal enterotoxin B.
Co-stimulation through CD28 is thought to be necessary for the activation of unprimed CD4+ T cells, which are otherwise rendered tolerant. However, we previously found that CD4+ T cell priming was normal or augmented in mice which overexpressed a soluble form of CTLA4 where co-stimulation through CD28 was abrogated. To investigate this CD4+ T cell response, we exploited the capacity of the superantigen staphylococcal enterotoxin B to stimulate T lymphocytes bearing V beta 8+, which represent approximately 30% of all CD4+ T cells. In litter-mate controls of CTLA4-Ig transgenic mice, immunization with staphylococcal enterotoxin B leads to expansion, followed by deletion of V beta 8+ T cells, and the remaining cells are tolerant when stimulated in vitro. Comparable expansion and deletion of V beta 8 T cells occurs in CTLA4-Ig transgenic mice. However, in contrast to normal mice, the remaining V beta 8+ T cells from CTLA4-Ig transgenic mice are not anergic and remain responsive to superantigen in vitro.
Lane
P
P
Basel Institute for Immunology, Switzerland.
Haller
C
C
McConnell
F
F
D000069594:Abatacept; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000235:genetics / Q000494:pharmacology*; D018122:B7-1 Antigen / Q000502:physiology*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D060908:CTLA-4 Antigen; D017635:Clonal Anergy / Q000187:drug effects / Q000502:physiology*; D004768:Enterotoxins / Q000276:immunology*; D007108:Immune Tolerance / Q000502:physiology*; D007114:Immunization; D018796:Immunoconjugates; D007136:Immunoglobulins / Q000235:genetics; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology*; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology*
D000942:Antigens, Bacterial; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D004768:Enterotoxins; D018796:Immunoconjugates; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; D000069594:Abatacept