Huchet R, Bruley-Rosset M, Mathiot C, Grandjon D, Halle-Pannenko O
INSERM U.267 Immunogénétique des Allogreffes, Hôpital Paul Brousse, Villejuif, France.
J Immunol. 1993 Mar 15;150(6):2517-24.
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.
研究了经历移植物抗宿主反应（GVH）的小鼠脾细胞对非H-2组织相容性抗原的抑制活性机制。在我们的模型中，通过将来自B10.D2（H-2d Mlsb）供体的骨髓和脾细胞注射到致死性照射的（DBA/2×B10.D2）F1（H-2d/d Mlsa/b）受体中来诱导GVH，这些受体仅在非H-2抗原方面存在差异。GVH脾细胞抑制对Con A和LPS的促有丝分裂反应，以及抗菠萝蛋白酶处理的小鼠红细胞（Br-MRBC）抗体反应。这种抑制是非特异性的且不受H-2限制，在用抗Thy-1加补体处理后没有改变。相反，在用L-亮氨酰甲酯处理后被消除。这些特征使得能够鉴定参与这种抑制类型的非T细胞、对L-亮氨酰甲酯敏感的细胞。GVH脾细胞介导的抑制与IFN-γ和转化生长因子-β1（TGF-β1）的活性相关（发现TGF-β1由GVH脾T细胞合成）。抗IFN-γ单克隆抗体消除了对Con A的促有丝分裂反应和抗Br-MRBC反应的抑制，并略微逆转了对LPS的促有丝分裂反应的抑制。抗TGF-β1抗体部分消除了对LPS的促有丝分裂反应的抑制，并完全消除了抗Br-MRBC反应的抑制，但对Con A的促有丝分裂反应的抑制没有改变。在与GVH相关的免疫抑制的潜在机制框架内讨论了这些结果。
