IL-7 prevents both caspase-dependent and -independent pathways that lead to the spontaneous apoptosis of i-IEL

Intestinal intraepithelial lymphocytes (i-IEL) readily undergo spontaneous apoptosis in vitro through an unclear mechanism. Here we examined the relat ionship between caspases, which plays a major role in apoptosis, and IL-7 i n the spontaneous apoptosis of i-IEL in vitro, We demonstrated that IL-7 an d zVAD prevented the spontaneous apoptosis of i-IEL by approximately 50% an d 25% respectively with no additive protection seen when both are used. IL- 7 preferentially prevented the apoptosis of gamma delta i-IEL, while zVAD e qually prevented the apoptosis of gamma delta and alpha beta i-IEL, Lastly, we demonstrated that the spontaneous apoptosis of i-IEL is associated with a marked increase in caspase activity. Caspase activity was completely inh ibited by zVAD, but only slightly by IL-7, Overall these results suggest th at two pathways lead to the spontaneous apoptosis of i-IEL, one which is ca spase dependent and the other which is caspase independent. IL-7 appears to exert its effect on i-IEL undergoing spontaneous by partially inhibiting b oth apoptotic pathways. (C) 2001 Academic Press.