Activation and peripheral expansion of murine T-cell receptor γδ intraepithelial lymphocytes

Background & Aims: The intestinal epithelial compartment is populated by CD8(+) alpha beta and gamma delta intraepithelial lymphocytes (IELs), which monitor the integrity of the epithelial barrier. alpha beta IELs are activated by peptide antigens presented by class I major histocompatibility complex (MHC) molecules, but it is unclear how gamma delta IELs are activated. Methods: G8 T-cell receptor (TCR) gamma delta transgenic (Tg) mice (specific for the class I MHC alloantigen, T22/10(b)) were crossed to class I MHC-deficient beta(2)-microglobulin-knockout (beta(2)m degrees) mice, and Tg(+) IELs were examined for relative yields and surface and functional phenotype. Results: Evidence for class I MHC-induced activation of Tg+ IELs was supported by the detection of 4-fold greater numbers of Tg+ IELs in GS x beta(2)m(+) mice that proliferated at 15-fold higher levels than IELs from G8 x beta(2)m degrees mice. However, expression of CD69, production of cytokine (interleukin 2 and interferon gamma), and detection of cytolytic function for IELs in G8 x beta(2)m degrees mice suggested that class I MHC was not required for gamma delta IEL development or maturation. Conclusions: These results suggest that CD8(+) TCR gamma delta IELs do not require class I MHC for development but support the notion that antigens presented by class I MHC molecules are involved in the peripheral expansion and differentiation of this subset.