Rejection of grafts without histocompatibility antigen disparity by TAP1−/− mice: a role for CD4+ t cells

• Published in: Transplantation proceedings 2004-05, Vol.36 (4), p.999-1000
• Main Authors: Marrero, I, Benvenutti, L.A, Noronha, I, Kalil, J, Coelho, V
• Format: Article
• Language: English
• Subjects: Animals; ATP-Binding Cassette Sub-Family B Member 2; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - physiology; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Graft Rejection - immunology; Graft Survival - immunology; H-2 Antigens - immunology; Lymphocyte Depletion - methods; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Skin Transplantation - immunology; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Time Factors; Tissue, organ and graft immunology
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2004.03.049

We have previously shown that TAP1−/− mice reject heart and skin grafts lacking an H-2 disparity. TAP1−/− mice, which are deficient for MHC-I molecules, probably have a T-cell repertoire with distinct reactivity to these molecules. We speculated that this rejection could be mediated by CD4+ T cells reactive to H-2 b class I molecules, or to class I–derived peptides presented by self-APC. This hypothesis was tested in the present work. Presensitization of TAP1−/− mice with H-2K b peptides accelerated the rejection of C57BL/6 (H-2 b) skin grafts (MST 13 days, P < .0057), indicating that these peptides were able to mobilize effector T cells that participate in rejection. In addition, CD4 T-cell depletion before transplantation induced a significant delay in rejection ( P < .0011), showing that CD4 T cells have a major role in the rejection process, though other cells may also contribute. In conclusion, these results support our hypothesis that H-2 b molecules may be targeted in graft rejection without an H-2 disparity. The low expression of MHC-I molecules on TAP1−/− mice may determine the selection of a T-cell repertoire that is reactive to self-MHC-I molecules, a phenomenon that is probably beyond the control of peripheral regulatory mechanisms.