Analysis of Intraepithelial Lymphocytes and Peyer’s Patch Lymphoid Tissue in TCR-Alpha Knockout Mice

Abstract

Despite numerous studies, attributing function to the distinct T cell receptor (TCR) αβ⁺ and TCR γδ+ IEL has proved difficult. TCR αβ⁺ cells are induced by the gut flora, have potent cytotoxic effector activity, and are capable of proliferation and elaborating lymphokines after stimulation in vitro.^1-4 In contrast the biological function of TCR γδ⁺ cells is still largely unknown, although these cells do have weak cytotoxic activity.^1-4 The stimulus which induces activity and the MHC restriction, if any, of TCR γδ⁺ IEL is unclear. Until now it has proved difficult to deplete IEL of all TCR αβ⁺ and yet retain sufficient TCR γδ⁺ IEL for functional assays at meaningful cell numbers. Several approaches have been taken with the aim of disrupting the T cell repertoire with varying degrees of success. The depletion of αβ T cells by injecting mice with antibodies to the αβ TCR, and the expression of prearranged TCR genes in transgenic mice are two examples.^5,6 Instead, we have used the approach of genetically deleting the capacity of mice to make TCR αβ⁺ T cells using the technique of homologous recombination.⁷ This system yields the cleanest model mouse host for studying the biological function of TCR γδ⁺ cells and in particular the role of TCR γδ⁺ cells in mucosal immunity.