Ka. Papadakis et al., The role of thymus-expressed chemokine and its receptor CCR9 on lymphocytes in the regional specialization of the mucosal immune system, J IMMUNOL, 165(9), 2000, pp. 5069-5076
Chemokines play an important role in the migration of leukocytes at sites o
f inflammation, and some constitutively expressed chemokines may direct lym
phocyte trafficking within lymphoid organs and peripheral tissues. Thymus-e
xpressed chemokine (TECK or Ck beta -15/CCL25), which signals through the c
hemokine receptor CCR9, is constitutively expressed in the thymus and small
intestine but not colon, and chemoattracts a small fraction of PBLs that c
oexpress the integrin alpha (4)beta (7). Here we show that TECK is expresse
d in the human small bowel but not colon by endothelial cells and a subset
of cells in intestinal crypts and lamina propria, CCR9 is expressed in the
majority of freshly isolated small bowel lamina propria mononuclear cells (
LPMC) and at significantly higher levels compared with colonic LPMC or PBL,
TECK was selectively chemotactic for small bowel but not colonic LPMC in v
itro. The TECK-induced chemotaxis was sensitive to pertussis toxin and part
ially inhibited by Abs to CCR9. TECK attracts predominantly the T cell frac
tion of small bowel LPMC, whereas sorted CD3(+)CCR9(+) and CD3(+)CCR9(-) ly
mphocytes produce similar Th1 or Th2 cytokines at the single cell level. Co
llectively, our data suggest that the selective expression of TECK in the s
mall bowel underlie the homing of CCR9(+) intestinal memory T cells to the
small bowel rather than to the colon. This regional specialization implies
a segregation of small intestinal from colonic immune responses.