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* Burns and Allen Research Institute and Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90048;
Univerity Hospital of Heraklion, University of Crete, Heraklion, Crete, Greece; and
Millennium Pharmaceuticals, Cambridge, MA 02139
The chemokine receptor CCR9 is expressed on most small intestinal lamina propria and intraepithelial lymphocytes and on a small subset of peripheral blood lymphocytes. CCR9-expressing lymphocytes may play an important role in small bowel immunity and inflammation. We studied the phenotype and functional characteristics of CCR9+ lymphocytes in blood from normal donors. A subset of CCR9+ T cells have a phenotype of activated cells and constitutively express the costimulatory molecules CD40L and OX-40. In contrast to CCR9-, CCR9+CD4+ peripheral blood T cells proliferate to anti-CD3 or anti-CD2 stimulation and produce high levels of IFN-
and IL-10. IL-10-producing cells were exclusively detected within the CCR9+ subset of CD4+ T cells by intracellular staining and were distinct from IL-2- and IFN--producing cells. Moreover, memory CCR9+CD4+ lymphocytes respond to CD2 stimulation with proliferation and IFN-/IL-10 production, whereas memory CCR9-CD4+ cells were unresponsive. In addition, memory CCR9+CD4+ T cells support Ig production by cocultured CD19+ B cells in the absence of prior T cell activation or addition of exogenous cytokines. Our data show that the memory subset of circulating CCR9+CD4+ T cells has characteristics of mucosal T lymphocytes and contains cells with either Th1 or T-regulatory 1 cytokine profiles. Studies on the cytokine profile and Ag specificity of this cell subset could provide important insight into small intestinal immune-mediated diseases and oral tolerance in humans.
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