Self-tolerance to transgenic γδ T cells by intrathymic inactivation

Abstract

DURING their intrathymic differentiation, T lymphocytes expressing αβ T-cell receptors (TCR) are negatively^1–3 and positively selected^4–8. 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 TL^b haplotype. Similar numbers of thymocytes expressing the transgenic TCR were generated in mice of TL^b and TL^d haplotypes. But γδ thymocytes from TL^b and TL^d transgenic mice differed in cell size, TCR density and in their capacity to respond to TL^b stimulator cells or interleukin-2 (IL-2). In contrast to γδ T cells from TL^d transgenic mice, γδ T cells from TL^b 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.