Central tolerance induction in natural immunoglobulin-allotype-specific T cells

Abstract

While self toleance is induced to IgGb2a in Ighb / b mice, an anti‐IgGb2a T cell activity emerges in their Igha / a congenic counterparts. This activity is revealed by postnatal transfer of Igha / a T splenocytes into Igha / b F1, in which total suppression of IgG2ab expression is established. Here, we sought to determine whether the natural T cell unresponsiveness to IgG2ab in Ighb / b mice involved a central tolerance. Based on the kinetics of postnatal thymic Cγ2ab gene expression in Ighb / b mice, we transplanted thymi from Ighb / b donors of diverse ages into tolerogen‐free Igha / a nu / nu recipients. The state of T cell tolerance or responsiveness to IgG2ab in these reconstituted nu / nu hosts was determined by monitoring the capacity of their splenocytes to induce suppression in Igha / b F1. These experiments demonstrated that: (i) in the Igha / a nu / nu recipients of adult Ighb / b thymi, 33 to 65 % T splenocytes were from nu / nu recipient origin, but these peripheral Igha / a T cells were rendered tolerant to IgG2ab during their differentiation through the adult Ighb / b thymi, (ii) circulating IgG2ab was not a prerequisite for this tolerance induction, (iii) Ighb / b thymic epithelium was unable to induce tolerance to IgG2ab and (iv) IgG2ab‐producing / presenting cells, colonizing the Ighb / b thymi, were certainly responsible of full tolerance induction to IgG2ab.

Activation and Tolerance in CD4+ T Cells Reactive to an Immunoglobulin Variable Region

“…Bogen et al (40) found that T cells specific for a V region peptide from the light chain of MOPC-315 underwent thymic deletion in mice that either expressed the cognate Ig or that were injected with soluble antibody at a high concentration. These results are consistent with others suggesting that wild-type IgG2a b -specific T cells attain tolerance in the thymus (41). In contrast, Granucci et al (7) found that IgG2a b -specific T cells from a TCR Tg mouse failed to undergo negative selection in mice endogenously expressing IgG2a b .…”

“…Evidence for central CD4 ϩ T cell tolerance to Ig sequences has been reported by several groups (38)(39)(40)(41)(42). However, two Tg systems previously developed to address this question yielded contrasting results.…”