In vivo activation of autoreactive cytotoxic T lymphocytes after bone marrow transplantation: evidence for the prethymic specificity of T cells?

The light density fraction (A + B, i.e., remaining above the 26% concentration in the discontinuous BSA gradient) of BCF1 (H-2b X H-2k) mouse bone marrow contains cells that after injection into irradiated syngeneic recipients give rise to autoreactive Lyt-2+, Thy-1+ CTL. After injection of unfractionated bone marrow cells, the levels of these CTL were low or undetectable, suggesting that either the precursors were highly enriched in the A + B fraction or that bone marrow cells with higher density have a suppressive function. The specificity of the killing was not directed toward all the available class I MHC antigens: only targets carrying H-2Kb-coded determinants were killed. There was no overlapping between the autoreactive and alloreactive precursors: cells from the A + B fraction could not respond to an alloantigen in vitro, not even in the presence of an interleukin 2-containing supernatant, and the autoreactive CTL activated in vivo could not kill allogeneic targets. The induction of the autoreactive CTL did not require the presence of the appropriate MHC antigen in the maturation environment, thus differing from the activation of mature T cells. The observed CTL specificity, together with the previous findings showing that prethymic T cells are locating in the same BSA fraction as the precursors for these autoreactive cells, support the idea that the prethymic T cell repertoire is, at least partially, directed to recognize self-MHC antigens.