Staphylococcal enterotoxin B as a potent suppressant of T lymphocytes: trace levels suppress T lymphocyte proliferative responses.
Staphylococcal enterotoxins have long been known to be powerful stimulators of T lymphocytes in mouse and man. In a previous study we showed that high concentrations of staphylococcal enterotoxin serotype B (SEB) failed to stimulate strong proliferative responses by Lewis rat T lymphocytes. Moreover, concentrations of SEB (10-50 micrograms/ml) that stimulated optimal mouse T lymphocyte proliferative responses suppressed a mitogen- or antigen-induced rat T lymphocytes proliferative responses. The present study shows that SEB at low concentrations (as low as 10(-3)-10(-4) micrograms/ml) and often also trace levels (about 10(-6)-10(-7) micrograms/ml) suppresses both rat and mouse T lymphocytes proliferative responses to mitogen or antigen. Furthermore, under different circumstances, SEB may have conflicting effects on the same T cells. While high concentrations (1-50 micrograms/ml) of SEB stimulate certain mouse T cell clones, low concentrations or trace levels have a potent suppressive effect on the same clones. The results indicate that the in vitro conflicting effects of SEB on the same T cells are concentration dependent and may reflect its in vivo effects on SEB-reactive T lymphocytes. The suppression of the mitogen- or antigen-induced stimulation of T cell clones by SEB was direct and did not require the agency of suppressor cells. Furthermore, the suppression by low amounts of SEB was not major histocompatibility complex restricted and affected a large proportion of both rat and mouse T lymphocyte subpopulation, regardless of their antigenic specificity. The concomitant suppressogenic and stimulatory characteristics of SEB support the conclusion that, under different conditions, SEB can be considered a "super-suppressogen" as well as a "super-antigen". Overall, the results suggest that SEB, and possibly other bacterial toxins, could be useful in immunomodulation of specific T cell responses.
Ben-Nun
A
A
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Yossefi
S
S
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D003208:Concanavalin A; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D004676:Myelin Basic Protein / Q000276:immunology; D012313:RNA / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects
D004768:Enterotoxins; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003208:Concanavalin A; C031818:enterotoxin B, staphylococcal; D012313:RNA