Clonal deletion of self-reactive T cells at the early stage of T cell development in thymus of radiation bone marrow chimeras

Sequential appearance of T cell subpopulations occurs in the thymocytes of irradiated C3H/He mice (H-2(k), Mls-1^b2^a, Thy-1.2) after transplantation with bone marrow cells of AKR/J mice (H-2(k), Mls-1^a-2^b, Thy-1.1) (AKR → C3H chimeras). The donor-derived thymocytes of AKR → C3H chimeras on day 14 after bone marrow transplantation (BMT) contained a large number of blastlike CD4⁺CD8⁺ cells which represent relatively immature thymocytes, whereas those on day 21 after BMT consisted of small sized CD4⁺CD8⁺ cells which represent a great part in normal thymocytes. To define the developmental stage at which clonal deletion of self-reactive T cells occurs in adult thymus, we followed the fate of Vβ6- or Vβ11-bearing T cells in the donor-derived thymocytes at the early stage of AKR → C3H chimeras. Mature thymocytes expressing high intensity of Vβ6 or Vβ11, which are involved in recognition of Mls-1^a or MHC I-E gene products, respectively, were deleted from the donor-derived thymocytes on day 21. Immature thymocytes expressing low intensity of Vβ6 in CD3(low) thymocyte fraction decreased in proportion, whereas those expressing low intensity of Vβ11 rather increased in proportion in the donor-derived thymocytes of AKR → C3H chimeras from day 14 to day 21 after BMT. These results suggest that the clonal deletion of Vβ6-positive cells occurs just at the stage of immature CD3(low)CD4⁺CD8⁺ cells, whereas the clonal deletion of Vβ11-positive cells may begin at the transitional stage from CD3(low)CD4⁺CD8⁺ cells to CD3(high) single positive cells. Timing of negative selection of thymocytes may vary in distinct T cells capable of recognizing different self-Ag.