Central tolerance induction in natural immunoglobulin-allotype-specific T cells.
While self toleance is induced to IgG(b)(2a) in Igh(b / b) mice, an anti-IgG(b)(2a) T cell activity emerges in their Igh(a / a) congenic counterparts. This activity is revealed by postnatal transfer of Igh(a / a) T splenocytes into Igh(a / b) F(1), in which total suppression of IgG(2a)(b) expression is established. Here, we sought to determine whether the natural T cell unresponsiveness to IgG(2a)(b) in Igh(b / b) mice involved a central tolerance. Based on the kinetics of postnatal thymic C(gamma2a)(b) gene expression in Igh(b / b) mice, we transplanted thymi from Igh(b / b) donors of diverse ages into tolerogen-free Igh(a / a) nu / nu recipients. The state of T cell tolerance or responsiveness to IgG(2a)(b) in these reconstituted nu / nu hosts was determined 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 / nu 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 tolerant 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 tolerance induction, (iii) Igh(b / b) thymic epithelium was unable to induce tolerance to IgG(2a)(b) and (iv) IgG(2a)(b)-producing / presenting cells, colonizing the Igh(b / b) thymi, were certainly responsible of full tolerance induction to IgG(2a)(b).
Majlessi
L
L
Unité d'Immunophysiologie Moléculaire, Institut Pasteur, Paris, France.
Sellier
C
C
Bordenave
G
G
D000818:Animals; D005803:Genes, Immunoglobulin; D007108:Immune Tolerance; D007126:Immunoglobulin Allotypes / Q000276:immunology*; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000637:transplantation; D014158:Transcription, Genetic
D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains