Inhibition of T Cell Alloreactivity by Bronchial Epithelium is Impaired in Lung Transplant Recipients, Through Pathways Involving TGF-[beta], IL-10 and HLA-G.

Background: Bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx) results from bronchial epithelial cell (BECs) damages, thought to be orchestrated by T cells primed by antigen-presenting cell (APC) presenting allo-antigens. In this cell cross-talk, BECs are also suspected to play a pivotal immunosuppressive role in T cell alloreactivity. We studied the immunomodulating role of BECs in a human ex-vivo model of allogeneic T cell response, both in healthy subjects and LTx recipients. Methods: BECs from 35 LTx recipients (n=22 stable, n=13 BOS]) and healthy controls (n=25) were cultured as primary cell cultures. Their inhibitory capacities through the involvement of tolerogenic molecules (human leukocyte antigen [HLA]-G, transforming-growth factor [TGF-[beta]], and interleukin [IL]-10) were tested on a mixed lymphocyte reaction between APCs and recipient T cells. Results: Control BECs inhibited T cell alloproliferation by a mean of 53+/-7%. This inhibitory effect of BECs was significantly reduced in the stable LTx group (24+/-8%, p=0.009), but not in the BOS TxP group (53+/-10%, p=0.97). Neutralization of HLA-G, TGF-[beta], and IL-10 partially restored T cell alloproliferation, arguing for their involvement in the immunosuppressive effect of BECs. BECs culture supernatant from stable LTx patients with impaired BEC properties showed a skewed Th2-type secretion profile (high IL-4/IFN-[gamma] ratio). Conclusion: The inhibitory properties of BECs are dysregulated in stable LTx recipients, which could suggest their instrumental role in the initiation of BOS process and potential targeted therapies. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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