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Dental Branch, Department of Basic Sciences, University of Texas Health Science Center, Houston, TX 77030
Murine small intestine intraepithelial lymphocytes (IELs) bear
properties of both activated and nonactivated T cells, although the
significance of that dichotomy remains unclear. In this study, we show
that although IELs express CD69 in situ and ex vivo, and have cytotoxic
activity ex vivo, most CD8+ IELs from normal mice are
phenotypically similar to naive T cells in that they are
CD45RBhigh, CD44low/int, and lack or have low
levels of expression of CD25, Ly-6C, OX40, Fas ligand (FasL),
and intracellular IFN-
synthesis. Unlike CD8+ lymph node
cells, IELs express high levels of the FasL gene, but do not express
surface FasL until after CD3-mediated stimulation has occurred.
Additionally, anti-CD3 stimulation of IELs in the presence of
actinomycin-D did not inhibit FasL expression, suggesting that
regulation FasL expression on IELs is controlled at least partially at
the posttranscriptional level. Following CD3-mediated stimulation, IELs
synthesize and secrete IFN- more rapidly and to greater levels than
CD8+ lymph node cells, and they acquire the phenotype of
fully activated effector cells as seen by an up-regulation of CD44,
Ly-6C, OX40, FasL, and CD25 with the kinetics of memory T cells, with
down-regulation of CD45RB expression. These findings indicate that
contrary to previous interpretations, most small intestine IELs are not
fully activated T cells, but rather that they are semiactivated T cells
ready to shift to a fully activated state once a CD3-mediated signal
has been received. These data also imply that under appropriate
conditions it is possible for T cells to be sustained in a state of
partial activation.
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