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.