Highly self-reactive naive CD4 T cells are prone to differentiate into regulatory T cells

Bruno Martin, Cédric Auffray, Arnaud Delpoux, Arnaud Pommier, Aurélie Durand, Céline Charvet, Philippe Yakonowsky, Hubert de Boysson, Nelly Bonilla, Alexandra Audemard, Tim Sparwasser, Benoit L. Salomon, Bernard Malissen and Bruno Lucas ()
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Bruno Martin: CNRS UMR8104, Cochin Hospital
Cédric Auffray: CNRS UMR8104, Cochin Hospital
Arnaud Delpoux: CNRS UMR8104, Cochin Hospital
Arnaud Pommier: CNRS UMR8104, Cochin Hospital
Aurélie Durand: CNRS UMR8104, Cochin Hospital
Céline Charvet: CNRS UMR8104, Cochin Hospital
Philippe Yakonowsky: CNRS UMR8104, Cochin Hospital
Hubert de Boysson: CNRS UMR8104, Cochin Hospital
Nelly Bonilla: CNRS UMR8104, Cochin Hospital
Alexandra Audemard: CNRS UMR8104, Cochin Hospital
Tim Sparwasser: Institute of Infection Immunology, TWINCORE Center of Experimental and Clinical Infection Research
Benoit L. Salomon: CNRS UMR7211, Pitié-Salpêtrière Hospital
Bernard Malissen: CNRS UMR6102, Aix-Marseille Université UM 631, 5 Campus de Luminy case 906
Bruno Lucas: CNRS UMR8104, Cochin Hospital

Nature Communications, 2013, vol. 4, issue 1, 1-12

Abstract: Abstract Upon activation, naive CD4 T cells differentiate into a variety of T-helper-cell subsets characterized by different cytokine production and functions. Currently, lineage commitment is considered to depend mostly on the environmental context to which naive CD4 T cells are exposed. Here we challenge this model based on the supposed homogeneity of the naive CD4 T-cell compartment. We show that peripheral naive CD4 T cells can be subdivided into two subsets according to Ly-6C expression. Furthermore, the two newly defined subsets (Ly-6C− and Ly-6C+ naive CD4 T cells) are not equal in their intrinsic ability to commit into the induced regulatory T-cell lineage. Finally, phenotypic analysis, imaging and adoptive transfer experiments reveal that Ly-6C expression is modulated by self-recognition, allowing the dichotomization of the naive CD4 T-cell compartment into two cell subsets with distinct self-reactivity. Altogether, our results show that naive CD4 T cells with the highest avidity for self are prone to differentiate into regulatory T cells.

Date: 2013
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DOI: 10.1038/ncomms3209

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