In vitro and in vivo T cell oligoclonality following chronic stimulation with staphylococcal superantigens.
Microbial superantigens (SAg), including SEB and TSST-1, polyclonally activate T cells belonging to specific TCR BV families. A pathogenic role for SAg in various human diseases has been suggested, but enthusiasm for this view has been tempered by the T cell oligoclonality in these disorders. To assess whether T cell oligoclonality can emerge following protracted SAg stimulation, human PBMC were stimulated with SEB, TSST-1, or anti-CD3 mAb and maintained in culture with exogenous IL-2. Oligoclonality was appreciated by day 14 among CD4(+) and CD8(+) T cells. In addition, mice transgenic for human DR2 and DQ8 were injected weekly with SEB, and splenic CD4(+) and CD8(+) T cells were analyzed for oligoclonality. In mice that received one or three such injections, little-to-no oligoclonality was detected. In contrast, considerable oligoclonality was detected in mice that received eight weekly SEB injections. Many of these T cell oligoclones were identical to "spontaneously" arising oligoclones detected in SEB-naive mice. Thus, T cell oligoclonality can emerge following chronic SAg stimulation. In hosts who have lost tolerance to self Ag, chronic exposure to SAg may preferentially promote expansion of autoreactive T cells and facilitate development of clinical disease.
D000818:Animals; D001427:Bacterial Toxins; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002999:Clone Cells; D022801:Complementarity Determining Regions / Q000235:genetics*; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics; D015802:HLA-DR2 Antigen / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D013154:Spleen / Q000276:immunology; D013210:Staphylococcus / Q000276:immunology*; D018089:Superantigens / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology
D001427:Bacterial Toxins; D022801:Complementarity Determining Regions; D004768:Enterotoxins; D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D015802:HLA-DR2 Antigen; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C031818:enterotoxin B, staphylococcal