T-CELLS WITH GAMMA DELTA T-CELL RECEPTORS (TCR) OF INTESTINAL-TYPE ARE PREFERENTIALLY EXPANDED IN TCR-ALPHA-DEFICIENT LPR MICE/

Fas-mediated apoptosis is essential for activation-induced cell death of alpha/beta T cells, but it is not clear what role, if any, it plays in regulating other components of the immune system. To study the rol e of Fas in gamma/delta T cell development, Fas-deficient lpr mice wer e bred with T cell receptor alpha gene-ablated (TCR-alpha -/-) mice to generate mice deficient in one or both genes. The TCR-alpha -/-, lpr/ lpr mice had a nearly 10-fold increase in total lymph node cell (LNC) number compared with Fas-intact TCR-alpha -/- mice, because of expansi on of TCR-gamma/delta(+) and TCR-beta(+) cells. In Fas-intact TCR-alph a -/- mice, approximately one third of the LNCs expressed TCR-gamma/de lta. These were evenly divided between the CD4(-), CD8-alpha(+) and th e CD4(-), CD8(-) subsets, and rarely expressed the B220 epitope of CD4 5. In contrast, in TCR-alpha -/-, lpr/lpr mice, TCR-gamma/delta(+) cel ls comprised half of the LNCs and were primarily CD4(-), CD8(-), and B 220(+). Moreover, Fas deficiency in TCR-alpha -/- mice caused a prefer ential expansion of gamma/delta T cells expressing variable region gen es characteristic of intestinal intraepithelial lymphocytes. These res ults demonstrate a role for Fas in regulating the gamma/delta T cell c ontribution to peripheral lymph nodes. This mechanism may be most impo rtant in limiting the access of activated intestinal intraepithelial l ymphocytes to the peripheral lymphoid system.