ELEVATED EXPRESSION OF BCL-2 AND BCL-X BY INTESTINAL INTRAEPITHELIAL LYMPHOCYTES - RESISTANCE TO APOPTOSIS BY GLUCOCORTICOIDS AND IRRADIATION

Administration of glucocorticoids or exposure to ionizing radiation in vivo results in a rapid cell death of thymocytes. We report that muri ne small intestinal intraepithelial lymphocytes (IEL) are resistant to both steroid- and radiation-induced deletion. This is due to resistan ce to apoptosis, as evidenced by the absence of detectable apoptotic I EL nuclei in situ after in vivo glucocorticoid treatment. IEL express normal levels of glucocorticoid receptors and these receptors bind [H- 3]dexamethasone to equivalent levels as other lymphocyte populations. Thus, their survival is due to post-receptor signaling mechanisms. Man y IEL express high levels of Bcl-2 and that of these BCl-2(high) IEL a re largely TCR gamma delta(+). Those IEL that do express high levels o f Bcl-2 are CD8 alpha(+)beta(-) CD4(-). In addition, IEL express Bcl-x , another protein shown to be involved in the protection of cells from apoptotic signals. IEL represent the first lymphocyte population in v ivo shown to have high levels of expression of both molecules, that ot herwise occur only in activated lymphocytes in vitro. These data sugge st that the Bcl-2(+)Bcl-x(+) IEL are activated cells and not an effete population of cells necessarily destined to die. Also, the high level s of Bcl-2 and Bcl-x in this in vivo activated population supports the in vitro correlate of protection from activation-induced cell death.