Involvement of IFN-gamma and transforming growth factor-beta in graft-vs-host reaction-associated immunosuppression.
The mechanisms of the suppressive activity of spleen cells from mice undergoing a graft-vs-host reaction (GVH) to non-H-2 histocompatibility Ag were investigated. In our model GVH is induced by injecting bone marrow and spleen cells from B10.D2 (H-2d Mlsb) donors into lethally irradiated (DBA/2 x B10.D2)F1 (H-2d/d Mlsa/b) recipients that differ only with regard to non-H-2 Ag. GVH spleen cells inhibit the mitogenic responses to Con A and LPS, as well as the anti-bromelain-treated mouse RBC (Br-MRBC) antibody response. This suppression was nonspecific and non-H-2-restricted and was not modified after treatment with anti-Thy-1 plus C. Conversely it was abrogated after treatment with L-leucyl methyl ester. These features permitted the identification of non-T cell, L-leucyl methyl ester-sensitive, cells involved in this type of suppression. The suppression mediated by GVH spleen cells was linked to the activity of IFN-gamma and transforming growth factor-beta 1 (TGF-beta 1) (TGF-beta 1 was found to be synthesized by GVH spleen T cells). mAb to IFN-gamma abrogated the suppression of the mitogenic response to Con A and the anti-Br-MRBC response and slightly reversed the suppression of the mitogenic response to LPS. Anti-TGF-beta 1 antibody partially abrogated the suppression of the mitogenic response to LPS and totally abrogated that of the anti-Br-MRBC response but left unmodified the suppression of the mitogenic response to Con A. These results are discussed within the framework of the mechanisms underlying the immunosuppression associated with GVH.
Huchet
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R
INSERM U.267 Immunogénétique des Allogreffes, Hôpital Paul Brousse, Villejuif, France.
Bruley-Rosset
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M
Mathiot
C
C
Grandjon
D
D
Halle-Pannenko
O
O
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D005260:Female; D006087:Graft vs Host Reaction / Q000276:immunology*; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013154:Spleen / Q000276:immunology; D013491:Suppressor Factors, Immunologic / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D013491:Suppressor Factors, Immunologic; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma