Cytolytic and IFN-gamma-producing activities of gamma-delta T cells in the mouse intestinal epithelium are T cell receptor-beta-chain dependent

We analyzed the cytolytic activity of intra-epithelial 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)-[Alpha][Beta] ([Alpha][Beta]-IEL) or TCR-[Gamma][Delta] ([Gamma][Delta]-IEL) were absent or markedly diminished. When compared with wild-type littermates, cytolytic activity of [Gamma][Delta]-IEL was sharply attenuated in TCR-[Beta] mutant mice but remained unaltered in TCR-[Alpha] mutant mice in which a minor population of dull TCR-[[Beta].sup.+] ([[Beta].sup.dim])-IEL was also present. Cytolytic activity of [Gamma][Delta]-IEL was maintained in mice doubly homozygous for [[Beta].sub.2]-microglobulin and transporter associated with antigen processing 1 gene mutations in which a conspicuous decrease was noted in absolute numbers of [Alpha][Beta]-IEL. In contrast, both TCR-[Delta] and IL-7 receptor-[Alpha] gene mutations that lead to lack of [Gamma][Delta]-IEL generation did not affect the development or cytolytic activity of the remaining [Alpha][Beta]-IEL. The anti-CD3 and anti-TCR-[Gamma][Delta] mAb-induced IFN-[Gamma] production of [Gamma][Delta]-IEL showed the same TCR-[Alpha] and TCR-[Beta] mutation-dependent variability. These results indicate that cytolytic and IFN-[Gamma]-producing activities of [Gamma][Delta] T cells in mouse intestinal epithelium are TCR-[Beta]-chain-dependent.