SELF-TOLERANCE TO TRANSGENIC-GAMMA-DELTA-T-CELLS BY INTRATHYMIC INACTIVATION

DURING their intrathymic differentiation, T lymphocytes expressing αβ T-cell receptors (TCR) are negatively1-3 and positively selected4-8. This selection contributes to the establishment of self-tolerance and ensures that mature CD4+ and CD8+ cell populations are restricted by the self major histocompatibility complex. Little is known, however, about γδ T-cell development. To investigate whether selection operates in the establishment of the γδ T-cell class, we have generated transgenic mice using γ- and δ-transgenes encoding a TCR that is specific for a product of a gene in the TL-region of the TLb haplotype. Similar numbers of thymocytes expressing the transgenic TCR were generated in mice of TLb and TLd haplotypes. But γδ thymocytes from TLb and TLd transgenic mice differed in cell size, TCR density and in their capacity to respond to TLb stimulator cells or interleukin-2 (IL-2). In contrast to γδ T cells from TLd transgenic mice, γδ T cells from TLb transgenic mice did not produce IL-2 and did not proliferate in response to TLb stimulator cells, but they did proliferate in the presence of exogenous IL-2. These results indicate that functional inactivation of self-antigen-specific T cells could contribute to the establishment of self-tolerance to thymic determinants. © 1990 Nature Publishing Group.