In Vivo Development of Transplant Arteriosclerosis in Humanized Mice Reflects Alloantigen Recognition and Peripheral Treg Phenotype of Lung Transplant Recipients. Issue 11 (29th July 2016)

• Record Type: Journal Article
• Authors: Siemeni, T.; Knöfel, A.‐K.; Madrahimov, N.; Sommer, W.; Avsar, M.; Salman, J.; Ius, F.; Frank, N.; Büchler, G.; Jonigk, D.; Jansson, K.; Maus, U.; Tudorache, I.; Falk, C. S.; Haverich, A.; Warnecke, G.
• Is Part Of: American journal of transplantation. Volume 16:Issue 11(2016:Nov.)
• Page Start: 3150
• Page End: 3162
• Publication Date: 2016-07-29
• Subjects: basic (laboratory) research/science -- clinical research/practice -- lung transplantation/pulmonology -- immunosuppression/immune modulation -- lung (allograft) function/dysfunction -- rejection: chronic -- alloantigen -- animal models: murine -- cytokines/cytokine receptors; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.13905
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : Experimentally, regulatory T cells inhibit rejection. In clinical transplantations, however, it is not known whether T cell regulation is the cause for, or an epiphenomenon of, long‐term allograft survival. Here, we study naïve and alloantigen‐primed T cell responses of clinical lung transplant recipients in humanized mice. The pericardiophrenic artery procured from human lung grafts was implanted into the aorta of NODrag −/− /IL‐2rγc −/− mice reconstituted with peripheral blood mononuclear cells (PBMCs) from the respective lung recipient. Naïve or primed allogeneic PBMCs procured 21 days post–lung transplantation with or without enriching for CD4 + CD25 high T cells were used. Transplant arteriosclerosis was assessed 28 days later by histology. Mice reconstituted with alloantigen‐primed PBMCs showed significantly more severe transplant arteriosclerosis than did mice with naïve PBMCs (p = 0.005). Transplant arteriosclerosis was equally suppressed by enriching for autologous naïve (p = 0.012) or alloantigen‐primed regulatory T cells (Tregs) (p = 0.009). Alloantigen priming in clinical lung recipients can be adoptively transferred into a humanized mouse model. Transplant arteriosclerosis elicited by naïve or alloantigen‐primed PBMCs can be similarly controlled by potent autologous Tregs. Cellular therapy with expanded autologous Tregs in lung transplantation might be a promising future strategy. Abstract : Naïve leukocytes from lung transplant recipients carry a strong alloreactive function that further increases following three weeks posttransplant in vivo priming, but this alloreactivity could be fully suppressed by higher autologous regulatory T cell numbers.