Major histocompatibility complex class II expression is required for posttransplant immunological but not hemopoietic reconstitution in mice.
We had previously shown in a canine model that the administration of anti-MHC class II monoclonal antibody (MAB) immediately after autologous marrow transplantation prevented hemopoietic reconstitution. Since MHC class II expression in mice differs from that in dogs we were interested in determining the effect of MHC class II manipulation on posttransplant hemopoietic and immunological recovery in mice. Three murine models including MHC class II knock-out mice were studied. BALB/c mice (I-E+, I-A+) given anti-MHC class II MAB H81.9 (anti-I-E; 1 mg/kg/day, days 0-4) after TBI and infusion of syngeneic marrow or infused with anti-I-E purged marrow both showed normal hemopoietic reconstitution. Similarly, C57B1/6 mice (I-E-, I-A+) transplanted with M5/114 (anti-I-A) purged marrow recovered normal hemopoiesis. MHC class II knock-out (C2D) mice, which lack class II completely, also recovered normal hemopoiesis after TBI and transplantation with either normal or class II-deficient (C2D) marrow, although the kinetics of platelet recovery as determined by megakaryocytopoiesis and platelet counts on day 14 were slightly delayed. C57B1/6 mice transplanted with C2D marrow recovered normally. Immunologic recovery, however, was abnormal both in C2D recipients and in normal mice transplanted with C2D marrow: While CD8+ T lymphocytes recovered normally, no (or only very few) CD4+ T cells were identified posttransplant. Treatment of normal mice with anti-MHC class II MAB in vivo or transplantation of MHC class II-purged marrow, however, did not interfere with complete immunological recovery, although T cell maturation was slightly delayed. Thus, complete immunological reconstitution requires the expression of MHC class II on marrow-derived precursor cells, while the expression of MHC class II antigens is not a requirement for hemopoietic reconstitution in mice.
Huss
R
R
Transplantation Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Beckham
C
C
Storb
R
R
Deeg
H J
HJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology / Q000528:radiation effects; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D017252:CD3 Complex / Q000032:analysis / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis / Q000276:immunology; D006410:Hematopoiesis / Q000276:immunology* / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000502:physiology; D016130:Immunophenotyping; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014181:Transplantation Immunology / Q000276:immunology*; D014916:Whole-Body Irradiation
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D000949:Histocompatibility Antigens Class II