Activation of T-cell receptor-gamma delta(+) cells in the intestinal epithelia of KN6 transgenic mice

We analysed the properties of intraepithelial lymphocytes of small intestin e (SI-IEL) in KN6-transgenic (Tg) mice expressing cDNA of T-cell receptor ( TCR)-gamma delta specific for the T22(b) molecule. While most splenic Tg TC R-gamma delta(+) cells from KN6-Tg mice with H-2(d/d) background (Tg(d/d) m ice) were Thy-1(+) CD8 alpha(-) CD44(dull+) CD45RB(+) CD69(-), Tg TCR-gamma delta(+) cells in SI-IEL (Tg gamma delta-IEL) were heterogeneous in the ex pression of Thy-1, CD8 alpha and CD44 molecules and predominantly CD45RB(+) CD69(+). Tg gamma delta-IEL exhibited a much reduced proliferative respons e to the antigen (irradiated H-2(b) splenocytes) than splenic Tg TCR-gamma delta(+) cells; the CD44(+) subset, but not the CD44(-) subset, in Tg gamma delta-IEL responded to the antigen. Furthermore, Tg gamma delta-IEL, but n ot splenic Tg TCR-gamma delta(+) cells, displayed cytolytic activity whethe r they were prepared from conventional or germ-free KN6-Tg mice. Comparativ e analysis of young and aged KN6-Tg mice revealed that the proportion of CD 44(+) cells in Tg gamma delta-IEL increased but the proliferative response of Tg gamma delta-IEL to the antigen attenuated in association with ageing. Moreover, although Tg gamma delta-IEL from Tg(b/d) mice contained a higher proportion of CD44(+) cells than Tg(d/d) mice, they did not respond to the antigen. These results demonstrate that Tg TCR-gamma delta(+) cells lose t he ability to recognize the antigen following activation in the intestinal epithelia.