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Tolerance to Maternal Immunoglobulins: Resilience of the Specific T Cell Repertoire in Spite of Long-Lasting Perturbations¹

Mathias Faure^2,*, Sébastien Calbo, Jean Kanellopoulos, Anne-Marie Drapier^*, Pierre-André Cazenave^* and Dominique Rueff-Juy^3,*

^* Unité d’Immunochimie Analytique (URA Centre National de la Recherche Scientifique 1961 and Université Pierre et Marie Curie), and Unité de Biologie Moléculaire du Gène, Institut Pasteur, Paris, France

T cell tolerance is established and maintained through various mechanisms, the critical component being the persistence of the specific Ag. However, at the molecular level, the nature of the recovering TCR repertoire following breakdown of tolerance is unknown. We address this important question by following light chain constant region (C)-specific CD4⁺ T cells of light chain knock-out (^-/-) mice born to ^+/- mothers. These cells, which were in contact with maternal ⁺ Igs from early ontogeny until weaning, were strongly tolerized. Tolerance was reversible and waned with the disappearance of peptide C_134–148 presentation in lymphoid organs, including the thymus. Whereas three specific Vß-Jß rearrangements emerged in the peptide C_134–148-specific CD4⁺ T cell response of all regular ^-/- mice, soon after breakdown of tolerance only one of these rearrangements was detected. The two others displayed a significant delay in reappearance and were still rare at 26 wk of age, while the control proliferative response had already recovered 3 mo earlier. At 52 wk of age, a complete recovery of the three canonical Vß-Jß rearrangements was observed. Thus, although profoundly perturbed for several months, the T cell repertoire returns to equilibrium, highlighting the resilient nature of this system.

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