Erosion of Transplantation Tolerance After Infection. Issue 1 (13th July 2016)

• Record Type: Journal Article
• Authors: Young, J. S.; Daniels, M. D.; Miller, M. L.; Wang, T.; Zhong, R.; Yin, D.; Alegre, M.‐L.; Chong, A. S.
• Is Part Of: American journal of transplantation. Volume 17:Issue 1(2017)
• Page Start: 81
• Page End: 90
• Publication Date: 2016-07-13
• Subjects: basic (laboratory) research/science -- immunosuppression/immune modulation -- animal models: murine -- infection and infectious agents -- bacterial -- tolerance: costimulation blockade -- tolerance: experimental; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.13910
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : Recent clinical studies suggest that operational allograft tolerance can be persistent, but long‐term surviving allografts can be rejected in a subset of patients, sometimes after episodes of infection. In this study, we examined the impact of Listeria monocytogenes (Lm) infection on the quality of tolerance in a mouse model of heart allograft transplantation. Lm infection induced full rejection in 40% of tolerant recipients, with the remaining experiencing a rejection crisis or no palpable change in their allografts. In the surviving allografts on day 8 postinfection, graft‐infiltrating cell numbers increased and exhibited a loss in the tolerance gene signature. By day 30 postinfection, the tolerance signature was broadly restored, but with a discernible reduction in the expression of a subset of 234 genes that marked tolerance and was down‐regulated at day 8 post‐Lm infection. We further demonstrated that the tolerant state after Lm infection was functionally eroded, as rejection of the long‐term surviving graft was induced with anti‐PD‐L1 whereas the same treatment had no effect in noninfected tolerant mice. Collectively, these observations demonstrate that tolerance, even if initially robust, exists as a continuum that can be eroded following bystander immune responses that accompany certain infections. Abstract : Young et al report that tolerance to allografts in a mouse model exists within a mechanistic continuum that, even if initially robust, can be eroded following bystander immune responses that accompany certain infections.