A role for Th2 cytokines in the suppression of CD8+ T cell-mediated graft rejection.
A major histocompatibility complex (MHC) class I-specific T cell receptor (TCR)-transgenic mouse was used to study classical-type transplantation tolerance in the adult. Engraftment of MHC class I-incompatible bone marrow and tolerance to donor-type skin grafts were obtained using dimethylmyeleran (DMM) as a myeloablative agent and a non-depleting anti-CD8 monoclonal antibody (mAb) as the sole immunosuppressant. Surprisingly, bone marrow engraftment was facilitated by host CD4+ T cells, a subset normally considered unable to reject class I MHC-incompatible grafts. A combination of mAb to interleukins (IL)-4 and -10 antagonized the "permissive" effects of host CD4+ T cells, indicating a possible role for Th2-type immunoregulation that can act on CD8+ T cells in this form of transplantation tolerance. The fate of graft-reactive T cells was monitored using anti-clonotypic antibodies. It was observed that bone marrow engraftment then led to peripheral deletion of mAb-blockaded, clonotype+ CD8+ T cells.
Scully
R
R
Department of Pathology, University of Cambridge, GB.
Cobbold
S P
SP
Mellor
A L
AL
Wissing
M
M
Arnold
B
B
Waldmann
H
H
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016026:Bone Marrow Transplantation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017637:Clonal Deletion; D016207:Cytokines / Q000502:physiology*; D006082:Graft Enhancement, Immunologic; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008808:Mice, Inbred CBA; D016038:Skin Transplantation / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000502:physiology*
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D016207:Cytokines