Internal regulation between constitutively expressed T cell co-inhibitory receptors BTLA and CD5 and tolerance in recent thymic emigrants

Immunologic self-tolerance involves signals from co-inhibitory receptors. Several T cell co-inhibitors, including PD-1, are expressed upon activation, whereas CD5 and BTLA are expressed constitutively. The relationship between constitutively expressed co-inhibitors and when they are needed is unknown. Deletion of <i>Btla</i> demonstrated BTLA regulates CD5 expression. Loss of BTLA signals, but not signalling by its ligand, HVEM, leads to increased CD5 expression. Higher CD5 expression set during thymic selection is associated with increased self-recognition, suggesting that BTLA might be needed early to establish self-tolerance. We found that BTLA and PD-1 were needed post-thymic selection in recent thymic emigrants (RTE). RTE lacking BTLA caused a CD4 T cell and MHC class II dependent multi-organ autoimmune disease. Together, our findings identify a negative regulatory pathway between two constitutively expressed co-inhibitors, calibrating their expression. Expression of constitutive and induced co-inhibitory receptors is needed early to establish tolerance in the periphery for RTE.

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Publication Details

Journal
Open Biology
Published
2024-10-01
DOI
https://doi.org/10.1098/rsob.240178
Citations
2
Primary Topic
Immune Cell Function and Interaction
Type
article
Field-Weighted Citation Impact
0.48

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article

Internal regulation between constitutively expressed T cell co-inhibitory receptors BTLA and CD5 and tolerance in recent thymic emigrants

Ting-Fang Chou, Julia F. May, Mitchell Kronenberg, Louis Boon et al.
2 citations
Open Biology
Immune Cell Function and Interaction
0.48
article

Internal regulation between constitutively expressed T cell co-inhibitory receptors BTLA and CD5 and tolerance in recent thymic emigrants

Ting-Fang Chou, Julia F. May, Mitchell Kronenberg, Louis Boon, Troy A. Baldwin, Kiyokazu Kakugawa, Hilde Cheroutre, Kristofor K. Ellestad, Govindarajan Thangavelu, Marcos Petersen, Adeolu Adegoke, Peter A. Bretscher, Qingyang Wang, Kevin Joannou, Colin C. Anderson
article en
2 citations

Abstract

Immunologic self-tolerance involves signals from co-inhibitory receptors. Several T cell co-inhibitors, including PD-1, are expressed upon activation, whereas CD5 and BTLA are expressed constitutively. The relationship between constitutively expressed co-inhibitors and when they are needed is unknown. Deletion of <i>Btla</i> demonstrated BTLA regulates CD5 expression. Loss of BTLA signals, but not signalling by its ligand, HVEM, leads to increased CD5 expression. Higher CD5 expression set during thymic selection is associated with increased self-recognition, suggesting that BTLA might be needed early to establish self-tolerance. We found that BTLA and PD-1 were needed post-thymic selection in recent thymic emigrants (RTE). RTE lacking BTLA caused a CD4 T cell and MHC class II dependent multi-organ autoimmune disease. Together, our findings identify a negative regulatory pathway between two constitutively expressed co-inhibitors, calibrating their expression. Expression of constitutive and induced co-inhibitory receptors is needed early to establish tolerance in the periphery for RTE.

Open BiologyVol. 14(10)
La Jolla Institute for Immunology (US), University of Alberta (CA), University of Saskatchewan (CA), University of California San Diego (US), RIKEN Center for Integrative Medical Sciences (JP)
American Association of Immunologists, University of Alberta, National Institutes of Health, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada
Good health and well-being
Openalex Percentile: Top 34%
Immune Cell Function and Interaction
0.48
DOIOpen Access PDFOpenAlex
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