T cells with γ/δ T cell receptors (TCR) of intestinal type are preferentially expanded in TCR-α-deficient lpr mice

Abstract

Fas-mediated apoptosis is essential for activation-induced cell death of α/β T cells, but it is not clear what role, if any, it plays in regulating other components of the immune system. To study the role of Fas in γ/δ T cell development, Fas-deficient lpr mice were bred with T cell receptor α gene-ablated (TCR-α-/-) mice to generate mice deficient in one or both genes. The TCR-α-/-, lpr/lpr mice had a nearly 10-fold increase in total lymph node cell (LNC) number compared with Fas-intact TCR-α-/- mice, because of expansion of TCR-γ/δ+ and TCR-β+ cells. In Fas-intact TCR-α-/- mice, approximately one third of the LNCs expressed TCR-γ/δ. These were evenly divided between the CD4-, CD8-α+ and the CD4-, CD8- subsets, and rarely expressed the B220 epitope of CD45. In contrast, in TCR-α-/-, lpr/lpr mice, TCR-γ/δ+ cells comprised half of the LNCs and were primarily CD4-, CD8- , and B220+. Moreover, Fas deficiency in TCR-α-/- mice caused a preferential expansion of γ/δ T cells expressing variable region genes characteristic of intestinal intraepithelial lymphocytes. These results demonstrate a role for Fas in regulating the γ/δ T cell contribution to peripheral lymph nodes. This mechanism may be most important in limiting the access of activated intestinal intraepithelial lymphocytes to the peripheral lymphoid system.