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 relationship between caspases, which plays a major role in apoptosis, and IL-7 in the spontaneous apoptosis of i-IEL in vitro. We demonstrated that IL-7 and zVAD prevented the spontaneous apoptosis of i-IEL by approximately 50% and 25% respectively with no additive protection seen when both are used. IL-7 preferentially prevented the apoptosis of γδ i-IEL, while zVAD equally prevented the apoptosis of γδ and αβ 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 inhibited by zVAD, but only slightly by IL-7. Overall these results suggest that two pathways lead to the spontaneous apoptosis of i-IEL, one which is caspase dependent and the other which is caspase independent. IL-7 appears to exert its effect on i-IEL undergoing spontaneous by partially inhibiting both apoptotic pathways.