Dynamic establishment of recipient resident memory T cell repertoire after human intestinal transplantationResearch in context
Wenyu Jiao,
Mercedes Martinez,
Constanza Bay Muntnich,
Julien Zuber,
Christopher Parks,
Aleksandar Obradovic,
Guangyao Tian,
Zicheng Wang,
Katherine D. Long,
Elizabeth Waffarn,
Kristjana Frangaj,
Rebecca Jones,
Alaka Gorur,
Brittany Shonts,
Kortney Rogers,
Guoyue Lv,
Monica Velasco,
Shilpa Ravella,
Joshua Weiner,
Tomoaki Kato,
Yufeng Shen,
Jianing Fu,
Megan Sykes
Affiliations
Wenyu Jiao
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, United States; Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Jilin, China
Mercedes Martinez
Department of Pediatrics, Columbia University, New York, NY, United States
Constanza Bay Muntnich
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, United States
Julien Zuber
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, United States
Christopher Parks
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, United States
Aleksandar Obradovic
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, United States
Guangyao Tian
Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Jilin, China
Zicheng Wang
Center for Computational Biology and Bioinformatics, Department of Systems Biology, Columbia University, New York, NY, United States
Katherine D. Long
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, United States
Elizabeth Waffarn
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, United States
Kristjana Frangaj
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, United States
Rebecca Jones
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, United States
Alaka Gorur
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, United States
Brittany Shonts
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, United States
Kortney Rogers
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, United States
Guoyue Lv
Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Jilin, China
Monica Velasco
School of Nursing, Columbia University, New York, NY, United States
Shilpa Ravella
Department of Medicine, Columbia University, New York, NY, United States
Joshua Weiner
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, United States; Department of Surgery, Columbia University, New York, NY, United States
Tomoaki Kato
Department of Surgery, Columbia University, New York, NY, United States
Yufeng Shen
Center for Computational Biology and Bioinformatics, Department of Systems Biology, Columbia University, New York, NY, United States
Jianing Fu
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, United States; Corresponding author. Columbia Center for Translational Immunology, 650 West 168th street, Black Building 1501A, New York, 10032, United States.
Megan Sykes
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, United States; Department of Surgery, Columbia University, New York, NY, United States; Department of Microbiology & Immunology, Columbia University, New York, NY, United States; Corresponding author. Columbia Center for Translational Immunology, 650 West 168th street, Black Building 1512, (Mailbox 127), New York, 10032, United States.
Summary: Background: Understanding formation of the human tissue resident memory T cell (TRM) repertoire requires longitudinal access to human non-lymphoid tissues. Methods: By applying flow cytometry and next generation sequencing to serial blood, lymphoid tissue, and gut samples from 16 intestinal transplantation (ITx) patients, we assessed the origin, distribution, and specificity of human TRMs at phenotypic and clonal levels. Findings: Donor age ≥1 year and blood T cell macrochimerism (peak level ≥4%) were associated with delayed establishment of stable recipient TRM repertoires in the transplanted ileum. T cell receptor (TCR) overlap between paired gut and blood repertoires from ITx patients was significantly greater than that in healthy controls, demonstrating increased gut-blood crosstalk after ITx. Crosstalk with the circulating pool remained high for years of follow-up. TCR sequences identifiable in pre-Tx recipient gut but not those in lymphoid tissues alone were more likely to populate post-Tx ileal allografts. Clones detected in both pre-Tx gut and lymphoid tissue had distinct transcriptional profiles from those identifiable in only one tissue. Recipient T cells were distributed widely throughout the gut, including allograft and native colon, which had substantial repertoire overlap. Both alloreactive and microbe-reactive recipient T cells persisted in transplanted ileum, contributing to the TRM repertoire. Interpretation: Our studies reveal human intestinal TRM repertoire establishment from the circulation, preferentially involving lymphoid tissue counterparts of recipient intestinal T cell clones, including TRMs. We have described the temporal and spatial dynamics of this active crosstalk between the circulating pool and the intestinal TRM pool. Funding: This study was funded by the National Institute of Allergy and Infectious Diseases (NIAID) P01 grant AI106697.
