PERIPHERAL DELETION OF AUTOREACTIVE CD8(+) T-CELLS IN TRANSGENIC MICE EXPRESSING H-2K(B) IN THE LIVER

The response of T cells specific for liver antigens was examined in transgenic mice expressing the allogeneic major histocompatibility complex class I molecule H-2K(b) (K-b) under the control of the sheep metallothionein promoter (Met-K-b mice). To follow the fate of K-b-specific T cells, and to prevent any aberrant thymic expression of the K-b transgene, the mice were thymectomized, lethally irradiated, protected with bone marrow cells from transgenic mice expressing in their T cells a K-b-specific T cell receptor identifiable by a clonotypic antibody, and given syngeneic non-transgenic thymus grafts. Although K-b-specific CD8(+) T cells were produced in the thymus grafts of these manipulated Met-K-b mice, only small numbers of such cells could be detected in the spleen and lymph nodes. The livers, however, showed signs of damage and were heavily infiltrated by actively dividing CD8(+) T cells. We provide strong evidence that the hepatocytes, not generally regarded as antigen-presenting cells, activated the K-b-specific CD8(+) T cells and that these disappeared after a vigorous autoimmune response that resulted in deletion.