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, and IL-10 Regulation1
Department of Basic Sciences, Dental Branch, University of Texas Health Science Center, Houston, TX 77030
The involvement of OX40 (CD134) in the activation of
CD8+ intestinal intraepithelial lymphocytes (IELs) has been
studied using freshly isolated IELs and in vitro CD3-stimulated IELs.
Although freshly isolated CD8+ IELs exhibited properties of
activated T cells (CD69 expression and ex vivo cytotoxicity), virtually
all CD8+ IELs from normal mice were devoid of other
activation-associated properties, including a lack of expression of
OX40 and the ligand for OX40 (OX40L) and an absence of intracellular
IFN-
staining. However, OX40 and OX40L expression were rapidly
up-regulated on CD8 IELs following CD3 stimulation, indicating that
both markers on IELs reflect activation-dependent events. Unlike IELs,
activated lymph node T cells did not express OX40L, thus indicating
that OX40-OX40L communication in the intestinal epithelium is part of a
novel CD8 network. Functionally, OX40 expression was exclusively
associated with IELs with active intracellular IFN- synthesis and
markedly enhanced cell-mediated cytotoxicity. However, OX40
costimulation during CD3-mediated activation significantly suppressed
IL-10 synthesis by IELs, whereas blockade of OX40-OX40L by
anti-OX40L mAb markedly increased IL-10 production. These findings
indicate that: 1) resident CD69+OX40- IELs
constitute a population of partially activated T cells poised for rapid
delivery of effector activity, 2) OX40 and OX40L expression defines
IELs that have undergone recent immune activation, 3) OX40+
IELs are significantly more efficient CTL than are OX40-
IELs, and 4) the local OX40/OX40L system plays a critical role in
regulating the magnitude of cytokine responses in the gut
epithelium.
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