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

While self toleance is induced to IgG(2a)(b), in Igh(b/b) mice, an anti-IgG (2a)(b), T cell activity emerges in their Igh(a/a) congenic counterparts. T his activity is revealed by postnatal transfer of Igh(a/a) T splenocytes in to Igh(a/b) F-1, in which total suppression of IgG(2a)(b) expression is est ablished. Here, we sought to determine whether the natural T cell unrespons iveness to IgG(2a)(b) in Igh(b/b) mice involved a central tolerance. Based on the kinetics of postnatal thymic C-gamma 2a(b) gene expression in Igh(b/ b) mice, we transplanted thymi from Igh(b/b) donors of diverse ages into to lerogen-free Igh(a/a) nu/nu recipients. The state of T cell tolerance or re sponsiveness to IgG(2a)(b) in these reconstituted nu/nu hosts was determine d by monitoring the capacity of their splenocytes to induce suppression in Igh(a/b) F-1. These experiments demonstrated that: (i) in the Igh(a/a) nu/n u recipients of adult Igh(b/b) thymi, 33 to 65 % T splenocytes were from nu /nu recipient origin, but these peripheral Igh(a/a) T cells were rendered t olerant to IgG(2a)(b) during their differentiation through the adult Igh(b/ b) thymi, (ii) circulating IgG(2a)(b) was not a prerequisite for this toler ance induction, (iii) Igh(b/b) thymic epithelium was unable to induce toler ance to IgG(2a)(b) and (iv) IgG(2a)(b)-producing/presenting cells, colonizi ng the Igh(b/b) thymi, were certainly responsible of full tolerance inducti on to IgG(2a)(b).