Diversity of the CD4 T Cell Alloresponse: The Short and the Long of It

Cell Reports
Jason AliG J Pettigrew

Abstract

MHC alloantigen is recognized by two pathways: "directly," intact on donor cells, or "indirectly," as self-restricted allopeptide. The duration of each pathway, and its relative contribution to allograft vasculopathy, remain unclear. Using a murine model of chronic allograft rejection, we report that direct-pathway CD4 T cell alloresponses, as well as indirect-pathway responses against MHC class II alloantigen, are curtailed by rapid elimination of donor hematopoietic antigen-presenting cells. In contrast, persistent presentation of epitope resulted in continual division and less-profound contraction of the class I allopeptide-specific CD4 T cell population, with approximately 10,000-fold more cells persisting than following acute allograft rejection. This expanded population nevertheless displayed sub-optimal anamnestic responses and was unable to provide co-stimulation-independent help for generating alloantibody. Indirect-pathway CD4 T cell responses are heterogeneous. Appreciation that responses against particular alloantigens dominate at late time points will likely inform development of strategies aimed at improving transplant outcomes.

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Citations

Dec 7, 2017·Current Opinion in Organ Transplantation·Jawaher AlsughayyirGavin J Pettigrew
Oct 18, 2016·Current Opinion in Nephrology and Hypertension·Thiago J BorgesLeonardo V Riella
Mar 19, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Chris WiebePeter W Nickerson
Feb 8, 2019·Frontiers in Immunology·Manu ChhabraGavin J Pettigrew
Jul 31, 2018·Journal of Immunology Research·Nina PilatThomas Wekerle
Nov 21, 2018·Frontiers in Immunology·Jacqueline H Y SiuGavin J Pettigrew
May 27, 2020·The Journal of Clinical Investigation·Stella Hw KhiewAnita S Chong
Dec 15, 2018·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Ines G HarperGavin J Pettigrew
Oct 4, 2017·Frontiers in Immunology·James S YoungAnita S Chong
Nov 7, 2019·Proceedings of the National Academy of Sciences of the United States of America·Michelle L MillerMaria-Luisa Alegre
Dec 1, 2017·Current Transplantation Reports·Michelle L MillerMaria-Luisa Alegre
Jun 21, 2020·Cellular Immunology·Jacqueline H Y SiuGavin J Pettigrew
Jan 24, 2019·Data in Brief·M Saeed QureshiGavin J Pettigrew
Feb 9, 2021·Journal of Immunological Methods·Naoki TanimineJames F Markmann

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Methods Mentioned

BETA
transgenic
flow cytometry
ELISA
FCS
FACS

Software Mentioned

FlowJo
FACSDiva

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