Neonatal thymus provides all the information required for tolerance induction against all the non-thymic organ-specific minor histocompatibility antigens

Using our original "in vivo MLR" technique, we demonstrated that B10.D2 cells grafted into irradiated (DBA/2 x B10.D2)F1 mice (H-2d/H-2d) were stimulated to divide by the whole non-H-2 minor histocompatibility antigens (MiHA) of the DBA/2 background in each organ where these MiHA are expressed. When B10.D2 cells were grafted into N7 mice (generation descending from six successive backcrosses with B10.D2 after an initial cross DBA/2 x B10.D2) which had kept 1/64 of the DBA/2 genetic background, a lack of correlation between the levels of stimulation in the different organs of the same mouse was demonstrated. We established that the number of expressed MiHA lies between 7 and more than 100, depending on the organ, and that the organ specificity is a feature of the expression of these MiHA. Furthermore, using a different technique, we demonstrated that B10.D2 T cells can acquire a specific tolerance state towards the whole DBA/2 antigen background throughout maturation and differentiation in a fully syngeneic environment with the exception of a neonate-(DBA/2 x B10.D2)F1 grafted thymus. We concluded, therefore, that all information corresponding to the adult- and organ-specific MiHA is available in the neonatal thymus. Three working hypotheses are proposed to reconcile the two lines of results.