Combined activation of murine lymphocytes with staphylococcal enterotoxin and interleukin-2 results in additive cytotoxic activity.
This report demonstrates that in vitro activation of murine spleen cells with interleukin-2 (IL-2) or the bacterial superantigen staphylococcal enterotoxin A (SEA) results in different patterns of activation and function of cytotoxic cells. Lymphokine-activated killer activity and antibody-dependent cellular cytotoxicity (ADCC) are mainly mediated by IL-2 activated natural killer (NK) cells. SEA is the most powerful T cell mitogen known so far and retargets cytotoxic T lymphocytes (CTL) to tumors expressing major histocompatibility complex (MHC) class II in staphylococcal-enterotoxin-dependent cellular cytotoxicity (SDCC). Culture of mouse spleen cells with SEA led to expansion and activation of T cells, which demonstrated strong SDCC activity and some NK-like cytotoxicity after 5 days in culture. Cell sorting revealed that both CD8+ and CD4+ T cells mediated SDCC but the former were more effective. Phenotypic analysis showed that SEA preferentially stimulated and expanded T cells expressing T cell receptor V beta 11, in particular CD8+ T cells. Combined activation with SEA and IL-2 resulted in simultaneous induction of T and NK cell cytotoxicity. Moreover, IL-2 had additive effects on SEA-induced SDCC. Combined treatment with SEA and IL-2 might therefore be an approach to induce maximal cytotoxicity against tumors and to recruit both T and NK cells in tumor therapy.
Belfrage
H
H
Department of Tumor Immunology, Wallenberg Laboratory, University of Lund, Sweden.
Bhiladvala
P
P
Hedlund
G
G
Dohlsten
M
M
Kalland
T
T
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004357:Drug Synergism; D004768:Enterotoxins / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004768:Enterotoxins; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal