Prevention of superantigen-induced tolerance in vivo by interleukin-2 treatment.
Injection of the superantigen staphylococcal enterotoxin A (SEA) activates both CD4+ and CD8+ T cells expressing certain families of T cell receptor (TCR) variable-region beta (V beta) chain. T cells respond with profound cytokine production and induction of cytotoxicity. Repeated injections, however, cause deletion and anergy of both CD4+ and CD8+ T cells, resulting in reduced frequency of SEA-responsive cells TCR-V beta11+ as well as reduced cytokine levels in serum upon challenge with SEA. Exogenous interleukin-2 (IL-2) in vivo rescued SEA-responsive CD4+ and CD8+ cells from SEA-induced deletion and/or increase expansion of SEA-primed cells as well as preventing downregulation of endogenous IL-2 production in vivo. Combined treatment with SEA and IL-2 also superinduced production of important cytokines for the cytotoxic function of T cells, tumour necrosis factor alpha, interferon gamma and IL-6, on a cellular level. These studies show that continuous stimulation with IL-2 in vivo could be useful for superantigen-based immunotherapy by induction of excessive T cell activation and by prevention of the development of T cell deletion and anergy.
Belfrage
H
H
Department of Cell and Molecular Biology, Lund University, Sweden.
Dohlsten
M
M
Hedlund
G
G
Kalland
T
T
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004338:Drug Combinations; D004768:Enterotoxins / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000187:drug effects*; D016130:Immunophenotyping; D007274:Injections, Intraperitoneal; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000494:pharmacology*
D016207:Cytokines; D004338:Drug Combinations; D004768:Enterotoxins; D007376:Interleukin-2; D011994:Recombinant Proteins; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal