Tolerance of thymocytes to allogeneic I region determinants encountered prethymically. Evidence for expression of anti-Ia receptors by T cell precursors before their entry into the thymus.

The present study has assessed whether precursor T cells express receptors specific for the recognition of allogeneic I region-encoded determinants before their entry into the thymus. Because the ability of thymocytes to proliferate in response to allogeneic stimulator cells was shown to primarily result from the recognition of allogeneic I region determinants, thymocytes must already express anti-Ia receptors. In contrast, the expression of anti- Ia receptors by functionally immature thymocyte precursors could not be directly assessed by mixed lymphocyte reaction reactivity. However, expression of anti-Ia receptors by thymocyte precursors could be assessed by their ability to be specifically tolerized by the allogeneic Ia determinants that they encountered during their differentiation. To determine whether T cell precursors could specifically recognize and be tolerized to allogeneic Ia determinants expressed prethymically, thymus- engrafted radiation bone marrow chimeras were constructed [A {arrow} A x B (Tx + A Thy)] such that strain A T cells would be differentiating within a syngeneic strain A thymus but would have been previously exposed to the allogeneic strain B Ia determinants of the irradiated A x B host. The strain A thymocytes from these experimental animals were indeed tolerant to the extrathymic allogeneic strain B Ia determinants expressed by the irradiated host. Such tolerance was not mediated by detectable suppression and was not explained by the presence intrathymically of extrathymic allogeneic Ia determinants. Thus, these results suggest that T cell precursors can be specifically tolerized entry into the thymus. In addition, the failure to detect the generation of thymocytes with specificity for the allogeneic Ia determinants of the irradiated host, which were not deleted prethymically, argues that novel anti-allo Ia receptor specificities are not generated intrathymically.