M. Faure et al., Tolerance to maternal immunoglobulins: Resilience of the specific T cell repertoire in spite of long-lasting perturbations, J IMMUNOL, 163(12), 1999, pp. 6511-6519
T cell tolerance is established and maintained through various mechanisms,
the critical component being the persistence of the specific Ag, However, a
t the molecular level, the nature of the recovering TCR repertoire followin
g breakdown of tolerance is unknown, We address this important question by
following kappa light chain constant region (C kappa)-specific CD4(+) T cel
ls of K light chain knock-out (kappa(-/-)) mice born to kappa(+/-) mothers.
These cells, which were in contact with maternal kappa(+) Igs from early o
ntogeny until weaning, were strongly tolerized, Tolerance was reversible an
d waned with the disappearance of peptide C kappa(134-148) presentation in
lymphoid organs, including the thymus, Whereas three specific VP-JP rearran
gements emerged in the peptide C kappa(134-148)(-) specific CD4(+) T cell r
esponse of all regular kappa(-/-) mice, soon after breakdown of tolerance o
nly one of these rearrangements was detected. The two others displayed a si
gnificant delay in reappearance and were still rare at 26 wk of age, while
the control proliferative response had already recovered 3 mo earlier. At 5
2 wk of age, a complete recovery of the three canonical V beta-J beta rearr
angements was observed. Thus, although profoundly perturbed for several mon
ths, the T cell repertoire returns to equilibrium, highlighting the resilie
nt nature of this system.