Significant MLR but not CTL responses against recipient antigens generated in T cells from bone marrow chimeras recovered from acute GVHD.
Lethally irradiated AKR mice received BMT from H-2D and minor lymphocyte stimulatory (Mls)-1 disparate B10.A mice. No GVHD signs were detected in AKR recipients of T cell-depleted BM cells (1 x 10(7)) alone ([B10.A --> AKR] T-). When B10.A splenic T cells (1 x 10(5)) were injected in addition to T cell-depleted BM cells ([B10.A --> AKR] T+), overt GVHD was observed. [B10.A --> AKR] T+ chimeras recovered from the GVHD 8 weeks after BMT. In T cells from these [B10.A --> AKR] T+ chimeras, a substantial population of Mls-1a-reactive Vbeta6+ T cells was present, whereas the Vbeta6+ cells were deleted in [B10.A --> AKR] T- chimeras. T cells from [B10.A --> AKR] T+ chimeras showed considerable MLR but no CTL response against AKR cells (split tolerance). Upon stimulation with AKR stimulators or anti-CD3 MoAb, T cells from [B10.A --> AKR] T+ chimeras produced significantly more IL-4 but significantly less IFN-gamma compared with those from [B10.A --> AKR] T- chimeras or unmanipulated B10.A mice. The serum level of IgG1 in [B10.A --> AKR] T+ chimeras was also significantly higher than that in [B10.A --> AKR] T- or B10.A mice. The present findings suggest that the split tolerance observed in BMT chimeras recovered from GVHD is attributable to the Th2 dominant state.
Morohashi
T
T
Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
Ogasawara
K
K
Kitaichi
N
N
Iwabuchi
K
K
Onoé
K
K
D000208:Acute Disease; D000818:Animals; D000941:Antigens / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002678:Chimera; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000941:Antigens; D016207:Cytokines; D007074:Immunoglobulin G