Prior viral infection primes cross-reactive CD8+ T cells that respond to mouse heart allografts.

Autor:	Khorki ME; Division of Nephrology & Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States., Shi T; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.; Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH, United States.; Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH, United States., Cianciolo EE; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States., Burg AR; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States., Chukwuma PC; Department of Chemistry & Biochemistry and the Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN, United States., Picarsic JL; Division of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.; Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, OH, United States., Morrice MK; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.; Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH, United States., Woodle ES; Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, United States., Maltzman JS; Department of Medicine, Stanford University, Palo Alto, CA, United States.; Geriatric Research and Education Clinical Center, Veterans Affairs (VA) Palo Alto Health Care System, Palo Alto, CA, United States., Ferguson A; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States., Katz JD; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.; Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH, United States., Baker BM; Department of Chemistry & Biochemistry and the Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN, United States., Hildeman DA; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.; Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Dec 08; Vol. 14, pp. 1287546. Date of Electronic Publication: 2023 Dec 08 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1287546
Abstrakt:	Introduction: Significant evidence suggests a connection between transplant rejection and the presence of high levels of pre-existing memory T cells. Viral infection can elicit viral-specific memory T cells that cross-react with allo-MHC capable of driving allograft rejection in mice. Despite these advances, and despite their critical role in transplant rejection, a systematic study of allo-reactive memory T cells, their specificities, and the role of cross-reactivity with viral antigens has not been performed. Methods: Here, we established a model to identify, isolate, and characterize cross-reactive T cells using Nur77 reporter mice (C57BL/6 background), which transiently express GFP exclusively upon TCR engagement. We infected Nur77 mice with lymphocytic choriomeningitis virus (LCMV-Armstrong) to generate a robust memory compartment, where quiescent LCMV-specific memory CD8 + T cells could be readily tracked with MHC tetramer staining. Then, we transplanted LCMV immune mice with allogeneic hearts and monitored expression of GFP within MHC-tetramer defined viral-specific T cells as an indicator of their ability to cross-react with alloantigens. Results: Strikingly, prior LCMV infection significantly increased the kinetics and magnitude of rejection as well as CD8 + T cell recruitment into allogeneic, but not syngeneic, transplanted hearts, relative to non-infected controls. Interestingly, as early as day 1 after allogeneic heart transplant an average of ~8% of MHC-tetramer + CD8 + T cells expressed GFP, in contrast to syngeneic heart transplants, where the frequency of viral-specific CD8 + T cells that were GFP + was <1%. These data show that a significant percentage of viral-specific memory CD8 + T cells expressed T cell receptors that also recognized alloantigens in vivo . Notably, the frequency of cross-reactive CD8 + T cells differed depending upon the viral epitope. Further, TCR sequences derived from cross-reactive T cells harbored distinctive motifs that may provide insight into cross-reactivity and allo-specificity. Discussion: In sum, we have established a mouse model to track viral-specific, allo-specific, and cross-reactive T cells; revealing that prior infection elicits substantial numbers of viral-specific T cells that cross-react to alloantigen, respond very early after transplant, and may promote rapid rejection. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors (BB and DH) declared that they are editorial board members at Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2023 Khorki, Shi, Cianciolo, Burg, Chukwuma, Picarsic, Morrice, Woodle, Maltzman, Ferguson, Katz, Baker and Hildeman.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu