The appearance of T cells bearing self-reactive T cell receptor in the livers of mice injected with bacteria

We demonstrated in the present study that with bacterial stimulation, an increased number of α/β T cells proliferated in the liver of mice and that even T cells bearing self-reactive T cell receptor (TCR) (or forbidden T cell clones), as estimated by anti-Vβ monoclonal antibodies in conjunction with immunofluorescence tests, appeared in the liver and, to some extent, in the periphery. The majority (>80%) of forbidden clones induced had double-negative CD4⁻8⁻ phenotype. In a syngeneic mixed lymphocyte reaction, these T cells appear to be self-reactive. Such forbidden clones and normal T cells in the liver showed a two-peak pattern ofTCR expression, which consisted of α/β TCR dull and bright positive cells, as seen in the thymus. A systematic analysis of TCR staining patterns in the various organs was then carried out. T cells from not only the thymus but also the liver had the two-peak pattern of α/β TCR, whereas all of the other peripheral lymphoid organs had a single-peak pattern of TCR. However, T cells in the liver were not comprised of double-positive CD4⁺8⁺ cells, which predominantly reside in the thymus. The present results therefore suggest that T cell proliferation in the liver might reflect a major extrathymic pathway for T cell differentiation and that this hepatic pathway has the ability to produce T cells bearing self-reactive TCR under bacterial stimulation, probably due to the lack of a double-positive stage for negative selection.