title: Resistance to tolerance induction in the diabetes-prone biobreeding rat as one manifestation of abnormal responses to superantigens.
abstract: T cells taken from normal rats treated with an exogenous source of bacterial superantigen in vivo specifically failed to proliferate following re-stimulation with the same superantigen in vitro. Responsiveness was restored following the addition of an exogenous source of interleukin-2 indicating that the T cells had been made functionally tolerant and not deleted. While staphylococcal enterotoxin treatment of normal rats virtually abolished T-cell proliferation to the same enterotoxin in vitro, T cells from similarly treated diabetes-prone Biobreeding (BB-DP) rats were markedly resistant to this in vivo effect. Responses in BB-DP rats were never reduced by more than 50% even when a 4 times more effective dose of enterotoxin was employed. The resistance of BB-DP peripheral T cells to staphylococcal enterotoxin-induced tolerance could not be attributed to differences in T-cell receptor V beta chain family usage of BB-DP vs normal T cells but was associated with qualitative differences in the way in which BB-DP T cells responded to staphylococcal enterotoxins in vitro. While under optimal stimulatory conditions BB-DP T-cell proliferative responses to staphylococcal enterotoxins appeared comparable to those from non-diabetes-prone animals, under superoptimal conditions BB-DP, but not diabetes-resistant, donor T-cell proliferative responses to staphylococcal enterotoxins could be blocked in vitro with antibodies to CD4 antigens. In addition, BB-DP T-cell proliferative responses were more sensitive to suboptimal staphylococcal enterotoxin doses in vitro. We discuss ways in which abnormal BB-DP T-cell responses to superantigens in general and resistance to staphylococcal enterotoxin-mediated tolerance induction in particular may play a role in the generation of a peripheral T-cell repertoire prone to autoimmunity.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, Denver, Colorado, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Sellins
authors.forename: D P
authors.initials: DP
authors.lastname: Gold
authors.forename: D
authors.initials: D
authors.lastname: Bellgrau
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology*; D007108:Immune Tolerance; D007700:Kinetics; D008213:Lymphocyte Activation; D016133:Polymerase Chain Reaction; D051381:Rats; D011913:Rats, Inbred BB; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D013211:Staphylococcus aureus; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C031818:enterotoxin B, staphylococcal