A role for Th2 cytokines in the suppression of CD8+ T cell-mediated graft rejection.

Journal article

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.

Authors: Scully, R; Cobbold, S; Mellor, A; Wissing, M; Arnold, B

• Publication status: Published
• Journal: European journal of immunology
• Volume: 27
• Issue: 7
• Pages: 1663-1670
• Publication date: 1997-07-01
• DOI: 10.1002/eji.1830270711
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: Cytokines; Clonal Deletion; Mice; Bone Marrow Transplantation; Skin Transplantation; CD8-Positive T-Lymphocytes; Antibodies, Blocking; CD4-Positive T-Lymphocytes; Graft Rejection; Spleen; Mice, Inbred CBA; Th2 Cells; Lymphocyte Depletion; Lymphocyte Activation; Animals; Graft Enhancement, Immunologic; Antibodies, Monoclonal; Immune Tolerance