Breakdown of T cell tolerance to IgG2a super(b) in Igh super(a) mice by de novo emerging anti-IgG2a super(b) T cells and not anergy reversion

• Published in: International immunology Vol. 9; no. 7; pp. 1053 - 1060
• Main Authors: Majlessi, L, Rujithamkul, N, Burlen-Defranoux, O, Bordenave, G
• Format: Journal Article
• Language: English
• Published: 01.07.1997
• ISSN: 0953-8178

The intrinsic T cell activity of Igh super(a) mice against IgG2a super(b) (IgG2a from the Igh super(b) haplotype) can be subjected to profound specific tolerance. In utero followed by post-natal exposure of Igh super(a) mice to soluble IgG2a super(b) results in the loss of the capacity of their T splenocytes to induce specific and chronic IgG2a super(b) allotype suppression in histocompatible Igh super(a/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 IgG2a super(b) tolerogen treatment was prolonged to 3, 6 or 9 months of age, T cell tolerance to IgG2a super(b) vanished and the capacity of Igh super(a) T splenocytes to induce IgG2a super(b) suppression in Igh super(a/b) recipients was systematically restored. The marked but partial thymus involution in 15-month-old Igh super(a) mice suggests the existence of some residual thymic output, capable of repopulating the anti-IgG2a super(b) 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-IgG2a super(b) 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 Igh super(a) T cells, parked in vivo, for up to 20 weeks in histocompatible tolerogen-free nu/nu mice.