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

Background and Aims: The intestinal epithelial compartment is populated by CD8⁺ αβ and γδ intraepithelial lymphocytes (IELs), which monitor the integrity of the epithelial barrier. αβ IELs are activated by peptide antigens presented by class I major histocompatibility complex (MHC) molecules, but it is unclear how γδ IELs are activated. Methods: G8 T-cell receptor (TCR) γδ transgenic (Tg) mice (specific for the class I MHC alloantigen, T22/10^b) were crossed to class I MHC-deficient β₂- microglobulin-knockout (β₂m°) 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 G8 x β₂m⁺ mice that proliferated at 15-fold higher levels than IELs from G8 x β₂m°mice. However, expression of CD69, production of cytokine (interleukin 2 and interferon gamma), and detection of cytolytic function for IELs in G8 x β₂m°mice suggested that class I MHC was not required for γδ IEL development or maturation. Conclusions: These results suggest that CD8⁺ TCR γδ 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.