Abstract
T cells must be activated and become effectors first before executing allograft rejection, a process that is regulated by diverse signals and transcription factors. In this study, we studied the basic leucine zipper ATF-like transcription factor (BATF) family members in regulating T cell activities in a heart transplant model and found that mice deficient for both BATF and BATF3 (Batf−/−Batf3−/− mice) spontaneously accept the heart allografts long-term without tolerizing therapies. Similarly, adoptive transfer of wild type T cells into Rag1−/− hosts induced prompt rejection of heart and skin allografts, whereas the Batf−/−Batf3−/− T cells failed to do so. Analyses of graft-infiltrating cells showed that Batf−/−Batf3−/− T cells infiltrate the graft but fail to acquire an effector phenotype (CD44highKLRG1+). Co-transfer experiments in a T cell receptor transgenic TEa model revealed that the Batf−/−Batf3−/− T cells fail to expand in vivo, retain a quiescent phenotype (CD62L+CD127+), and unable to produce effector cytokines to alloantigen stimulation, which contrasted sharply to that of wild type T cells. Together, our data demonstrate that the BATF and BATF3 are critical regulators of T effector functions, thus making them attractive targets for therapeutic interventions in transplant settings.
Original language | English (US) |
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Pages (from-to) | 414-426 |
Number of pages | 13 |
Journal | American Journal of Transplantation |
Volume | 22 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2022 |
Keywords
- Allografts/metabolism
- Animals
- Basic-Leucine Zipper Transcription Factors/genetics
- Gene Expression Regulation
- Interferon Regulatory Factors
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- T-Lymphocytes/metabolism
ASJC Scopus subject areas
- Transplantation
- Pharmacology (medical)
- Immunology and Allergy