Specific inhibition of hybrid resistance in F1 hybrid mice pretreated with parent-strain spleen cells. II. Evidence for an Hh-1 antigen-specific tolerization.
Lethally irradiated F1 mice reject bone marrow graft from H-2b parents. In a previous paper we showed that pretreatment of F1 hybrid with H-2b parental spleen cells abrogates this hybrid resistance (HR) to parental bone marrow growth by inducing a Thy-1+Lyt-1+2- nylon-adherent suppressor cell. We studied the mechanism of induction of this suppressor cell. Two hypotheses were tested; both were based on the observation that parental spleen cells when injected into a F1 hybrid, recognize the alloantigens of the opposite parent and proliferate; the proliferation of these Hh-1+ cells may result in an overload of the pretreated F1 hybrids with Hh-1 Ag, and in the development of a graft-vs-host reaction that is followed by a non-specific immunodeficiency (GVHID). Thus abrogation of HR could be due to either a tolerization with high doses of Hh-1 Ag or the GVHID. Our results show that abrogation of HR does not correlate with the GVHID because 1) it is induced after pre-treatment with H-2b parental cells only, whereas GVHID is observed after injection with cells from either of the two parents; and 2) it is induced in several conditions where GVHID does not occur; after pre-treatment with 1000-rad-irradiated or T-cell depleted or only class I incompatible spleen cells or with spleen cells from nude parents as well as after pre-treatment with H-2b bone marrow cells. HR is overcome by the injection of H-2Db homozygous or of cross-reactive H-2Ds homozygous cells only. However, although pretreatment with H-2Db homozygous spleen cells is necessary, it is not sufficient for an efficient overcoming of HR. Indeed enhancement of H-2b bone marrow growth after pre-treatment with 1000-rad-irradiated, T-cell depleted or nude parent spleen cells is very short-lasting and never reaches the level observed after pre-treatment with normal spleen cells. We conclude that inhibition of HR in F1 hybrids pretreated with parental spleen cells is not a consequence of a GVHID but of a specific tolerization with Hh-1 Ag; however, the HR is inhibited more consistently when inoculum used for the pretreatment contains fully immunocompetent T cells. The role of the immunocompetent parental T cells in abrogation of HR is discussed.
Kosmatopoulos
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K
INSERM U.267, Hôpital Paul Brousse, Villejuif, France.
Scott-Algara
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D
Halle-Pannenko
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O
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D016026:Bone Marrow Transplantation; D003433:Crosses, Genetic; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance; D007113:Immunity, Innate; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D008819:Mice, Nude; D011995:Recombination, Genetic; D013154:Spleen / Q000276:immunology*
D000939:Epitopes; D006183:H-2 Antigens; C056907:Hh1 protein, mouse; D006649:Histocompatibility Antigens