Longitudinal assessment of T cell inhibitory receptors in liver transplant recipients and their association with posttransplant infections |
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Authors: | Krupa R. Mysore Rafik M. Ghobrial Sunil Kannanganat Laurie J. Minze Edward A. Graviss Duc T. Nguyen Katherine K. Perez Xian C. Li |
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Affiliation: | 1. Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA;2. Immunobiology & Transplant Science Center, Houston Methodist Hospital, Houston, TX, USA;3. Department of Surgery, Weill Cornell Medical College of Cornell University, New York, NY, USA;4. Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston, TX, USA;5. Department of Pharmacy, Houston Methodist Hospital, Houston, TX, USA |
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Abstract: | Current immunosuppression regimens in organ transplantation primarily inhibit T cells. However, T cells are also critical in protective immunity, especially in immune‐compromised patients. In this study, we examined the association of T cell dysfunction, as marked by expression of T cell exhaustion molecules, and posttransplant infections in a cohort of liver transplant patients. We focused on Programmed Death 1 (PD‐1) and T cell Ig‐ and mucin‐domain molecule 3 (Tim‐3), which are potent co‐inhibitory receptors, and their persistent expression often leads to T cell dysfunction and compromised protective immunity. We found that patients with the highest expression of PD‐1 +Tim‐3+ T cells in the memory compartment before transplantation had increased incidence of infections after liver transplantation, especially within the first 90 days. Longitudinal analysis in the first year showed a strong association between variability of PD‐1 and Tim‐3 expression by T cells and infectious episodes in transplant patients. Furthermore, T cells that expressed PD‐1 and Tim‐3 had a significantly reduced capacity in producing interferon (IFN)‐γ in vitro, and this reduced IFN‐γ production could be partially reversed by blocking PD‐1 and Tim‐3. Interestingly, the percentage of Foxp3+ regulatory T cells in liver transplant patients was stable in the study period. We concluded that the functional status of T cells before and after liver transplantation, as shown by PD‐1 and Tim‐3 expression, may be valuable in prognosis and management of posttransplant infections. |
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Keywords: | cell death: exhaustion costimulation immunobiology infectious disease liver disease: infectious liver transplantation/hepatology T cell biology translational research/science |
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