Activation and re-activation potential of T cells responding to staphylococcal enterotoxin B.
To elucidate the parameters that lead to superantigen induced non-responsiveness, an in vitro model for studying primary and secondary responses to the bacterial superantigen staphylococcal enterotoxin B (SEB) was established. Upon re-activation with SEB, in vitro SEB primed T cells show an early proliferative response that 'quenches' in time and is severely impaired 3 days after re-stimulation. Despite their overall impaired proliferative capacity and IL-2 production, these T cells are able to produce IFN-gamma and to up-regulate activation markers CD69 and IL-2R alpha upon re-stimulation with SEB, demonstrating that SEB non-responsiveness is not absolute. Rather, it reflects the inability to mount an ongoing proliferative response upon re-stimulation with SEB. Our results also demonstrate that SEB-induced non-responsiveness is not simply the result of presentation in the absence of co-stimulation, since presentation of SEB on highly purified dendritic cells during the primary response did not prevent the induction of non-responsiveness. As previously shown, SEB induces a Th1 phenotype in responding CD4+ T cells. Skewing towards a Th2 phenotype by adding IL-4 and antibodies to IFN-gamma did not prevent the induction of non-responsiveness by SEB. Interestingly, T cells pretreated with plate-bound anti-CD3 epsilon and anti-V beta 8 were also non-responsive to SEB re-stimulation. Thus, non-responsiveness to SEB (defined here as inability to produce IL-2 and proliferate) seems to reflect an intrinsic inability of previously activated T cells to respond to SEB, probably reflecting differences in signal transduction pathways used by naive versus previously activated T cells.
Division of Immunology, The Netherlands Cancer Institute, Amsterdam.
M E
ME
Hamel
E E
EE
Eynon
H F
HF
Savelkoul
A
A
van Oudenaren
A M
AM
Kruisbeek
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology*; D005434:Flow Cytometry; D007108:Immune Tolerance; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000819:agonists / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D018418:Th2 Cells / Q000378:metabolism
D004768:Enterotoxins; D007376:Interleukin-2; D018089:Superantigens; D015847:Interleukin-4; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma