Spontaneous breakdown of T cell tolerance in the mouse lgG2ab-suppression model despite long-term tolerogenesis since the perinatal period

• Published in: International immunology 1996-10, Vol.8 (10), p.1627-1636
• Main Authors: Majlessi, Laleh, Rujithamkul, Nipa, Sellier, Christèle, Bordenave, Guy
• Format: Article
• Language: English
• Subjects: Ig allotype; in vivo animal models; repertoire development; TCR
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/8.10.1627

T celt-induced fgG2ab allotype suppression provides a physiological model for the study of T cell responsiveness or tolerance to this Ig allotype. Normal, untreated mice of the lgha haplotype possess a basic and easily amplifiable T cell reactivity against the expression of lgG2ab, while their lghb congenic mice produce substantial levels of this Ig and thereby are tolerant to this self-protein antigen. Therefore, the involved TCR repertoire in lgha and lghb congenic mice is different. We have previously shown, in lghb and Igha/b mice perinatally deprived of lgG2ab expression, that T lymphocytes bearing anti-lgG2ab TCR can emerge and induce an autoimmune suppression of lgG2ab. Correlatively, full and lgG2ab-specific T cell tolerance can be induced in lgha mice by their perinatal exposure to this Ig allotype. In this physiological model, which involves neither superantigens nor TCR-transgenic T cells, the responsive or tolerant state in lgha mice is assessed in vivo by the capacity to induce or not a T CD8+-dependent suppression of lgG2ab allotype production in Igha/b recipients of these cells. Taking advantage of this system, we were able to demonstrate here that, over the long term, this perinatally induced, lgG2ab-specific T cell tolerance was not definitively acquired, and that a spontaneous and total tolerance breakdown was observed by the age of 6 months. Furthermore, we showed that perinatal followed by prolonged tolerogen treatments up to 3, 6 and even 9 months of age were no longer sufficient to assure definitive T cell tolerance acquisition to lgG2ab, as the T cell suppression-induction capacity of lgha mice was partially and then entirely restored 3–6 months after the end of the tolerogen administration.