Prevention of murine acute graft-versus-host disease by staphylococcal enterotoxin B treatment.
Retroviral superantigens such as minor lymphocyte stimulating (Mls) antigen play an important role in the pathogenesis of acute graft-versus-host disease (GVHD). However, it remains unclear how exogenous bacterial superantigens modulate acute GVHD. In this study, we tested the effects of staphylococcal enterotoxin B (SEB) on the development of acute GVHD in a model involving the systemic transfer of parental C57Bl/6 spleen cells into BDF1 mice. SEB treatment suppressed the expansion of donor-derived T cells and blocked the decrease in the number of host cells. Impaired haematopoiesis was actually rescued by treatment with SEB. In SEB-treated mice, both spontaneous proliferation and IL-2 production in T cells were suppressed on day 2 after parental cell infusion. On day 21, the number of donor-derived CD4+ Vbeta8+ T cells markedly decreased in the spleen of SEB-treated mice. Donor-derived CD4+ T cells failed to proliferate in response to host alloantigens, and both donor- and host-derived T cells were unable to produce IL-2 in response to concanavalin A stimulation, suggesting that SEB treatment induced a general immunosuppressive state. Our results indicate that SEB treatment prevents the development of acute GVHD by leading to unresponsiveness of donor-derived T cells against host alloantigens in a Vbeta-restricted and unrestricted manner.
Takenaka
K
K
Department of Internal Medicine, Medical Coordination Centre and Blood Services Division,Shiga University of Medical Science, Seta-Tukinowa, Otsu, Japan.
Fujiyama
Y
Y
Andoh
A
A
Sasaki
T
T
Amakata
Y
Y
Matsubara
H
H
Hodohara
K
K
Bamba
T
T
D000208:Acute Disease; D000818:Animals; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D006410:Hematopoiesis / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013211:Staphylococcus aureus / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D004768:Enterotoxins; D007166:Immunosuppressive Agents; D016693:Receptors, Antigen, T-Cell, alpha-beta; C031818:enterotoxin B, staphylococcal