Mechanisms of Development of αβ T Cell Antigen Receptor-Bearing Cells in γδ T Cell Antigen Receptor Transgenic Mice

Our lab has generated transgenic mice that carry the genes encoding a γδ T cell antigen receptor (γδ TCR) from a γδ T cell clone with known specificity. This γδ T cell clone, G8, was derived from a BALB/c nu/nu mouse by alloantigen stimulation (Matis et al. (1987)). G8 is specific for an MHC class-Mike gene that maps to the TL region of the H-2 locus (Bluestone et al. (1988)). G8 is typical of γδ T cells that derive from the adult thymus or spleen in that it is negative for the CD4 and CD8 T cell markers, and uses a Vγ2-Jγ1-Cγ1- encoded γ chain for its TCR. Recently (Dent et al. (1990)), we have used these γδ TCR transgenic mice to study whether self-reactive γδ T cells are tolerized in a similar way as T cells that bear the αβ T cell antigen receptor (αβ T cells). In transgenic mice that did not bear the TL-encoded ligand (H-2d/d) , CD4/CD8 negative γδ T cells bearing the G8 specificity were found in the lymph nodes and spleen. In transgenic mice that expressed the TL-encoded ligand (H-2b/d) , transgenic γδ T cells were eliminated from the peripheral lymphoid organs, although Vγ2-positive cells persisted in the thymus. This phenotype would imply that a deletion process is occuring similar to that shown for self-reactive αβ T cells.