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+ Intestinal Intraepithelial Lymphocytes1
*
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; and
Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan
TCR
+ cells are enriched in the intestine mucosa
and constitute approximately half of the intestinal intraepithelial
lymphocytes (iIEL) in mice. They are likely activated by self and
foreign Ags in situ, but little is known about how the activated
iIEL are regulated. In the iIEL compartment, IL-2 is produced by
activated TCR
ß+ iIEL, and IL-15 message is detected in
iIEL and in the epithelial cells. We found surface expression of IL-2
as well as IL-15Rs on activated iIEL, and examined the effects
of IL-2 and IL-15 on the survival and death of iIEL during
secondary stimulation through TCR. We found that both cytokines
supported growth of the restimulated iIEL, but exerted different
effects on their survival. A significant higher number of live cells
were recovered from the 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 found no difference in the levels of Bcl-2 and Bax proteins
between the two groups. However, the level of Bcl-xL
protein diminished with time in the IL-2 group whereas the level was
sustained in the IL-15 group, which may contribute to the pro-survival
effect of IL-15. These results demonstrated that the survival of
activated iIEL is differentially regulated by IL-2 and
IL-15.
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