Topic 2 lecture note..

cells express CCR5 and CXCR3 and E7 and can migrate to the gut epithelium where
they interact with E-cadherin. For B cells, local production in Peyer’s patches of BLC
may be important. Accumulation of eosinophils involves LFA-1/ICAM-1, VLA-
4/VCAM-1, and 47/MAdCAM-1/L-selectin, perhaps influenced by eotaxin produced
by mononuclear cells.
Animals deficient in 7 integrins fail to accumulate T cells in the gastrointestinal tract,
and Peyer’s patches, because 47 is missing. SLC (which binds CCR7) stimulates
47-mediated adhesion of lymphocytes to MAdCAM-1. Defects in CCR7 or SLC
produce mice with reduced numbers of T cells in secondary lymphoid organs, including
Peyer’s patches. For B cells, BLC is important, as mice deficient in the BLC receptor
CXCR5 fail to develop normal Peyer’s patches. But SLC and BLC are not restricted to
the gut, hence are important in homing to lymph nodes in general. TECK, however, is
produced by small intestinal epithelial cells, but not by skin or lymph nodes, or by other
regions of the colon. It is mostly expressed in the crypt region most closely associated
with MAdCAM-1 expressing vessels. TECK has been detected on small intestinal
endothelium. Its receptor CCR9 is expressed on virtually all T cells in the small intestine,
and on memory CD4+ T cells, especially those expressing high levels of 47, whereas
it is not on other memory CD4 + T cells. The GI tract represents the largest reservoir of
eosinophils within the body. Eosinophils have the same pattern of adhesion molecules,
but don’t express either E7, or the chemokine receptors found on gut-homing T cells.
CCR3-active chemokines appear to be responsible for eosinophil accumulation. Eotaxindeficient
mice have few eosinophils within the villae of the intestine.