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

Background & Aims: The intestinal epithelial compartment is populated by CD 8(+) alpha beta and gamma delta intraepithelial lymphocytes (IELs), which m onitor the integrity of the epithelial barrier. alpha beta IELs are activat ed by peptide antigens presented by class I major histocompatibility comple x (MHC) molecules, but it is unclear how gamma delta IELs are activated. Me thods: 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-def icient beta(2)-microglobulin-knockout (beta(2)m degrees) mice, and Tg(+) IE Ls were examined for relative yields and surface and functional phenotype. Results: Evidence for class I MHC-induced activation of Tg+ IELs was suppor ted 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 bet a(2)m degrees mice. However, expression of CD69, production of cytokine (in terleukin 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 requi red for gamma delta IEL development or maturation. Conclusions: These resul ts 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 m olecules are involved in the peripheral expansion and differentiation of th is subset.