Peripheral deletion of autoreactive CD8+ T cells in transgenic mice expressing H-2Kb 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-2Kb (Kb) under the control of the sheep metallothionein promoter (Met-Kb mice). To follow the fate of Kb-specific T cells, and to prevent any aberrant thymic expression of the Kb transgene, the mice were thymectomized, lethally irradiated, protected with bone marrow cells from transgenic mice expressing in their T cells a Kb-specific T cell receptor identifiable by a clonotypic antibody, and given syngeneic non-transgenic thymus grafts. Although Kb-specific CD8+ T cells were produced in the thymus grafts of these manipulated Met-Kb 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 Kb-specific CD8+ T cells and that these disappeared after a vigorous autoimmune response that resulted in deletion.
Bertolino
P
P
Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, Victoria, Australia.
Heath
W R
WR
Hardy
C L
CL
Morahan
G
G
Miller
J F
JF
D000818:Animals; D001854:Bone Marrow Cells; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002470:Cell Survival; D017637:Clonal Deletion; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000276:immunology*; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D011828:Radiation Chimera; D013950:Thymus Gland / Q000166:cytology
D006183:H-2 Antigens