Studies of T cell deletion and T cell anergy following in vivo administration of SEB to normal and lupus-prone mice.
This study examines the responses of lupus-prone NZB, (NZB x NZW) F1, BXSB, MRL-lpr/lpr and control mice (H-2 and Mls matched) to in vivo administration of the superantigen staphylococcal enterotoxin B (SEB). Two weeks after i.v. administration of 500 micrograms SEB, CD4+V beta 8+ lymph node T cells were deleted equivalently by lupus-prone and control mice. However, IE+ strains deleted a greater proportion (47% to 77%) of their CD4+V beta 8+ cells than did IE- strains (24% to 27%). CD8+V beta 8+ cells were deleted less than CD4+V beta 8+ cells by injection of 500 micrograms SEB. IE- strains failed to delete CD8+V beta 8+ cells, whereas six of seven IE+ strains deleted > 25% of their CD8+V beta 8+ cells. IE+ MRL-lpr/lpr mice showed some impairment in deletion: they failed to delete CD8+V beta 8+ cells at all doses of SEB and had reduced deletion of CD4+V beta 8+ cells at low doses of in vivo SEB (10 and 50 micrograms). Peripheral expansion of the intrathymically deleted V beta 7 TCR family was not observed in lupus-prone mice 2 wk after 500 micrograms in vivo SEB. In vitro restimulation with SEB of mice previously injected with 500 micrograms SEB demonstrated anergy in T cells from all strains, including the IE- and MRL-lpr/lpr. This result contrasts with previous reports of tolerance defects in lupus-prone strains using B cell read-out assays as measures of tolerance. The present study demonstrates that there is no global defect in peripheral T cell deletion or anergy in lupus-prone mice to the superantigen SEB. Although additional Ag would need to be studied, these experiments raise the possibility that some reported tolerance defects in lupus-prone strains may reflect excessive B cell responses to relatively normal T cell signals.
Scott
D E
DE
Cellular Immunology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892.
Kisch
W J
WJ
Steinberg
A D
AD
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013211:Staphylococcus aureus / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C031818:enterotoxin B, staphylococcal