International Immunology, Vol 9, 1053-1060, Copyright © 1997 by Oxford University Press
L Majlessi, N Rujithamkul, O Burlen-Defranoux and G Bordenave
The intrinsic T cell activity of Igha mice against IgG2ab (IgG2a from the
Ighb haplotype) can be subjected to profound specific tolerance. In utero
followed by post-natal exposure of Igha mice to soluble IgG2ab results in
the loss of the capacity of their T splenocytes to induce specific and
chronic IgG2ab allotype suppression in histocompatible Igha/b recipients.
However, this full T cell tolerance has not been definitively acquired as
it is spontaneously reversed when investigated 3-6 months after the end of
the tolerogen treatment. Even when the IgG2ab tolerogen treatment was
prolonged to 3, 6 or 9 months of age, T cell tolerance to IgG2ab vanished
and the capacity of Igha T splenocytes to induce IgG2ab suppression in
Igha/b recipients was systematically restored. The marked but partial
thymus involution in 15- month-old Igha mice suggests the existence of some
residual thymic output, capable of repopulating the anti-IgG2ab peripheral
T pool subsequent to tolerogen clearance. In the present study, we showed
that the mechanisms of this tolerance and its reversion involve, at the end
of tolerogen treatment, the physical elimination or the irreversible
inactivation of natural anti-IgG2ab T cell clones and their replacement,
but neither the establishment of reversible anergy nor the recruitment of T
cells which could actively maintain tolerance. The spontaneous breakdown of
this T cell unresponsiveness was effectively prevented when de novo T cell
maturation was inhibited by thymectomy at the end of tolerogen
administration. Moreover, tolerance reversion did not occur in peripheral
mature Igha T cells, parked in vivo, for up to 20 weeks in histocompatible
tolerogen-free nu/nu mice.
ARTICLES
Breakdown of T cell tolerance to IgG2ab in Igha mice by de novo emerging anti-IgG2ab T cells and not anergy reversion
Unite d'Immunophysiologie Moleculaire, Institut Pasteur, Paris, France.
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