Cytolytic and IFN-γ-producing activities of γδ T cells in the mouse intestinal epithelium are T cell receptor-β-chain dependent

We analyzed the cytolytic activity of intraepithelial T cells (IEL) isolated from the small intestines of 2- to 3-month-old mutant mice rendered deficient in different gene(s) in which the number of IEL expressing either T cell receptor (TCR)-αβ (αβ-IEL) or TCR-γδ (γδ-IEL) were absent or markedly diminished. When compared with wild-type littermates, cytolytic activity of γδ-IEL was sharply attenuated in TCR-β mutant mice but remained unaltered in TCR-α mutant mice in which a minor population of dull TCR-β(+) (β(dim))-IEL was also present. Cytolytic activity of γδ-IEL was maintained in mice doubly homozygous for β(2)-microglobulin and transporter associated with antigen processing 1 gene mutations in which a conspicuous decrease was noted in absolute numbers of αβ-IEL. In contrast, both TCR-δ and IL-7 receptor-α gene mutations that lead to lack of γδ-IEL generation did not affect the development or cytolytic activity of the remaining αβ-IEL. The anti-CD3 and anti-TCR-γδ mAb-induced IFN-γ production of γδ-IEL showed the same TCR-α and TCR-β mutation-dependent variability. These results indicate that cytolytic and IFN-γ-producing activities of γδ T cells in mouse intestinal epithelium are TCR-β-chain-dependent.