TCR signaling events are required for maintaining CD4 regulatory T cell numbers and suppressive capacities in the periphery.
CD4 regulatory T cells (Tregs) can be subdivided into two subsets according to Ly-6C expression in the periphery. Phenotypic analysis, imaging, and adoptive-transfer experiments of peripheral Ly-6C(-) and Ly-6C(+) Tregs reveal that the nonexpression of Ly-6C by ∼70% of peripheral Tregs depends on TCR signaling events. Interestingly, Ly-6C(-) Tregs express higher surface amounts of key immunosuppressive molecules than do Ly-6C(+) Tregs and produce constitutively anti-inflammatory cytokines. In line with their phenotype, Ly-6C(+) Tregs exhibit poor suppressive capacities in vitro and in vivo. Finally, although Ly-6C(-) Tregs maintain their numbers with age, Ly-6C(+) Tregs gradually disappear. Altogether, our data strongly suggest that both the survival and suppressive functions of peripheral CD4 Tregs rely on their ability to receive strong TCR signals.
Institut Cochin, Centre National de la Recherche Scientifique UMR8104, INSERM U1016, Université Paris Descartes, 75014 Paris, France.
Arnaud
A
Delpoux
Institut Cochin, Centre National de la Recherche Scientifique UMR8104, INSERM U1016, Université Paris Descartes, 75014 Paris, France.
Philippe
P
Yakonowsky
Institut Cochin, Centre National de la Recherche Scientifique UMR8104, INSERM U1016, Université Paris Descartes, 75014 Paris, France.
Aurélie
A
Durand
Institut Cochin, Centre National de la Recherche Scientifique UMR8104, INSERM U1016, Université Paris Descartes, 75014 Paris, France.
Céline
C
Charvet
Institut Cochin, Centre National de la Recherche Scientifique UMR8104, INSERM U1016, Université Paris Descartes, 75014 Paris, France.
Michael
M
Valente
Institut Cochin, Centre National de la Recherche Scientifique UMR8104, INSERM U1016, Université Paris Descartes, 75014 Paris, France.
Arnaud
A
Pommier
Institut Cochin, Centre National de la Recherche Scientifique UMR8104, INSERM U1016, Université Paris Descartes, 75014 Paris, France.
Nelly
N
Bonilla
Institut Cochin, Centre National de la Recherche Scientifique UMR8104, INSERM U1016, Université Paris Descartes, 75014 Paris, France.
Bruno
B
Martin
Institut Cochin, Centre National de la Recherche Scientifique UMR8104, INSERM U1016, Université Paris Descartes, 75014 Paris, France.
Cédric
C
Auffray
Institut Cochin, Centre National de la Recherche Scientifique UMR8104, INSERM U1016, Université Paris Descartes, 75014 Paris, France bruno.lucas@inserm.fr.
Bruno
B
Lucas
D000367:Age Factors; D000375:Aging / Q000276:immunology; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D056747:Immunomodulation; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
D000950:Antigens, Ly; D000954:Antigens, Surface; C494192:Ly-6C antigen, mouse; D011948:Receptors, Antigen, T-Cell