Peripheral deletion of autoreactive CD8+ T cells in transgenic mice expressing H‐2Kb in the liver

Abstract

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.