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

Abstract

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)-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+ (betadim)-IEL was also present. Cytolytic activity of gamma delta-IEL was maintained in mice doubly homozygous for beta2-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.