Ishikawa H, Saito K, Kubota E
Department of Microbiology, Keio University School of Medicine, Tokyo, Japan.
J Immunol. 1989 Mar 1;142(5):1495-9.
Our previous study revealed that in F1 mice raised by crossing C3H/He or AKR/J mice with various H-2-congenic B10-series strains, parental H-2k spleen cells (SC) could not induce the graft-vs-host reaction (GvHR)-associated immunosuppression (GAIS). We also elucidated that a limited number of non-H-2 genes of parental C3H/He or AKR/J mice that had been incorporated into the F1 hybrids determined the F1 resistance to the GAIS, and the present study was done to explore the mechanism implicated in this type of F1 resistance to GAIS. SC from B10.AL mice carrying an rH-2 (K:k I:k S:k D:d) haplotype but not SC from H-2K B10.BR (k k k k) mice induced GAIS of in vitro CTL responses to third-party alloantigens in H-2k/d (C3H/He x B10.D2)F1 recipients mice. Further, SC from H-2k/a (C3H/He x B10.A)F1 mice carrying heterozygous C3H/B10 non-H-2 background but not SC from the same H-2k/a (B10.BR x B10.A)F1 mice but carrying homozygous B10/B10 background induced GAIS in H-2k/d (C3H/He x B10.D2)F1 recipients. Although C3H/He-, B10.BR-, and C3H.OH (d d d k)-SC were incapable of inducing GAIS in (C3H/He x B10.D2)F1 (k/d k/d k/d k/d) recipients, they were all good inducers of GAIS in (C3H.OH x B10.BR)F1 (d/k d/k d/k k/k) recipients. Exactly the same pattern of co-operative non-H-2 AKR and H-2D region-gene control of GAIS was observed on GvHR induced in H-2k/d (AKR/J x B10.D2)F1 recipients. These results suggest that the non-H-2 genes of C3H/He or AKR/J strain inhibit the functional expression of certain antigenic determinant(s) when it is encoded by heterozygous but not homozygous gene(s) linked tightly to H-2D region of k haplotype. Thus, the F1 resistance to GAIS is mediated by immune response of F1 recipients who miss the antigenic determinant(s) against that expressed on cell surface of GvHR-inducing T lymphocytes.
我们之前的研究表明，在用C3H/He或AKR/J小鼠与各种H-2同源B10系列品系杂交培育的F1小鼠中，亲代H-2k脾细胞（SC）不能诱导移植物抗宿主反应（GvHR）相关的免疫抑制（GAIS）。我们还阐明，亲代C3H/He或AKR/J小鼠中少量已整合到F1杂种中的非H-2基因决定了F1对GAIS的抗性，本研究旨在探索这种F1对GAIS抗性所涉及的机制。携带rH-2（K:k I:k S:k D:d）单倍型的B10.AL小鼠的SC能诱导H-2k/d（C3H/He×B10.D2）F1受体小鼠对第三方同种异体抗原的体外CTL反应的GAIS，而H-2K B10.BR（k k k k）小鼠的SC则不能。此外，携带杂合C3H/B10非H-2背景的H-2k/a（C3H/He×B10.A）F1小鼠的SC能诱导H-2k/d（C3H/He×B10.D2）F1受体小鼠产生GAIS，而携带纯合B10/B10背景的同一H-2k/a（B10.BR×B10.A）F1小鼠的SC则不能。虽然C3H/He-、B10.BR-和C3H.OH（d d d k）-SC不能在（C3H/He×B10.D2）F1（k/d k/d k/d k/d）受体小鼠中诱导GAIS，但它们在（C3H.OH×B10.BR）F1（d/k d/k d/k k/k）受体小鼠中都是良好的GAIS诱导剂。在H-2k/d（AKR/J×B10.D2）F1受体小鼠中诱导的GvHR上观察到完全相同的GAIS的非H-2 AKR和H-2D区域基因协同控制模式。这些结果表明，当由与k单倍型的H-2D区域紧密连锁的杂合而非纯合基因编码时，C3H/He或AKR/J品系的非H-2基因会抑制某些抗原决定簇的功能表达。因此，F1对GAIS的抗性是由F1受体的免疫反应介导的，这些受体缺少针对GvHR诱导性T淋巴细胞细胞表面表达的抗原决定簇。
