94 Gamma Delta T Cells Contribute to Acute and Chronic Allograft Rejection Via IL-17 Induced Inflammation in a Murine Heart Transplantation Model

• Published in: The Journal of heart and lung transplantation Vol. 30; no. 4; p. S39
• Main Authors: Kimura, N, Nakae, S, Itoh, S, Merk, D.R, Gong, Y, Wang, X, Patlolla, B, Neophytou, E, Chang, P.A, Robbins, R.C, Fischbein, M.P
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 2011
• Subjects: Surgery
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2011.01.101

Purpose The role of gamma delta (GD) T cells in allograft rejection remains poorly understood. We have reported that IL-17 contributes to allograft rejection in a murine heart transplant model. Because intragraft GD T cells are the predominant source of IL-17, we hypothesized GD T cells may play a key role in allograft rejection. Methods and Materials Acute rejection: FVB donor hearts heterotopically transplanted into (a) GD T cell-deficient C57BL/6 (TCR G−/− ) or (b) C57BL/6 (WT) recipients. Graft survival measured. Graft infiltrating cells detected with FACS analysis. Neutrophil activity accessed via myeloperoxidase (MPO) assay. Cytokine mRNA expression detected with Taqman PCR. Chronic rejection: C-H-2bm12 KhEg (H-2bm12 ) donor hearts transplanted into (a) TCR G−/− or (b) WT recipients. Graft survival assessed with graft beating scores (0 to 4). Grafts harvested day 52 and graft coronary artery disease (GCAD) evaluated with morphometric analysis (luminal occlusion, intima-to-media ratio, and percentage of diseased vessels). Graft infiltrating cells assessed by FACS. Results Acute model: Graft survival was prolonged in TCR G−/− recipients (n = 18) compared to WT recipients (n = 14) (14.4±8.2 days vs. 8.6±1.2 days, p < 0.01). Graft infiltrating CD45+ , CD4+ , CD8+ cells, neutrophils, and MPO activity were decreased in TCR G−/− recipients (p < 0.05). FACS analysis revealed GD T cells were key IL-17 producers (WT); IL-17 producing cells were decreased in TCR G−/− recipients (p < 0.05). Supporting these findings, IL-17 and IL-23 mRNA expression was decreased in TCR G−/− recipients (p < 0.05). Chronic model: Graft survival was improved in TCR G−/− recipients, and GCAD development was reduced in TCR G−/− recipients. Graft infiltrating CD45+ cells were attenuated in TCR G−/− recipients (p < 0.05). Conclusions GD T cells are (1) crucial for the development of acute and chronic allograft rejection during heart transplants, (2) key producers of IL-17, and (3) important in inflammatory cell recruitment.