Differential effects of IL-2 and IL-15 on the death and survival of activated TCR gamma delta(+) intestinal intraepithelial lymphocytes

TCR gamma delta(+) cells are enriched in the intestine mucosa and constitut e approximately half of the intestinal intraepithelial lymphocytes (iIEL) i n mice. They are likely activated by self and foreign Ags in situ, but litt le is known about how the activated gamma delta iIEL are regulated. In the iIEL compartment, IL-2 is produced by activated TCR alpha beta(+) iIEL, and IL-15 message is detected in iLEL and in the epithelial cells, We found su rface expression of IL-2 as well as IL-15Rs on activated gamma delta iIEL, and examined the effects of IL-2 and IL-15 on the survival and death of gam ma delta iIEL during secondary stimulation through TCR, We found that both cytokines supported growth of the restimulated gamma delta iIEL, but exerte d different effects on their survival. A significant higher number of live cells were recovered from the gamma delta iIEL cultures restimulated in IL- 15 than in IL-2. Quantitation of apoptotic cells showed more cell death in the IL-2 group than in the IL-15 group, The cell death was associated with restimulation through TCR and was not caused by insufficient growth factor, thus representing activation-induced cell death. Western blot analyses fou nd no difference in the levels of Bcl-2 and Bar proteins between the two gr oups. However, the level of Bcl-x(L), protein diminished with time in the I L-2 group whereas the level was sustained in the IL-15 group, which may con tribute to the pro-survival effect of IL-15. These results demonstrated tha t the survival of activated gamma delta iIEL is differentially regulated by IL-2 and IL-15.