Regulation of cell death and survival in intestinal intraepithelial lymphocytes

Intraepithelial lymphocytes (IEL) of the small murine bower represent a uni que population of mostly CD8(+) T lymphocytes that reside within the epithe lial cell layer of the intestinal mucosa. The close interaction with epithe lial cells appears to be crucial for IEL survival since isolation and ex vi vo culture induces massive apoptosis in this lymphocyte population. Here, w e provide evidence that this form of IEL cell death may be mediated at leas t in part by endogenously produced glucocorticoids since adrenalectomy or t reatment of mice with a glucocorticoid receptor antagonist significantly en hanced ex vivo survival of IEL, We further demonstrate that ex vivo activat ion of IEL induces upregulation of anti-apoptotic gene products, compensate s for the lack of survival cytokines and rescues from apoptotic cell death, Thus, similar to thymocytes and T cell hybridomas, IEL survival may be reg ulated by the antagonistic action of TCR activation and glucocorticoids.