CD4+CD3- cells induce Peyer's patch development:: role of α4β1 integrin activation by CXCR5

CD4(+)CD3(+) cells are the predominant hematopoietic cells found in mouse fetal intestine. We prove their role as Peyer's patch(PP)-inducing cells by transfer into neonatal PP-deficient mice. To test the requirement of chemokines and adhesion molecules in induction of PIP, we studied mice deficient in CXCR5 and/or alpha4beta1 integrin-mediated adhesion. CXCR5(-/-) mice have CD4(+)CD3 cells, which are inefficient in inducing PIP formation. We show here that CXCR5/CXCL13 signaling activates alpha4beta1 integrin on CD4(+)CD3(+) cells. Blocking of beta1 integrin or VCAM-1, the ligand of alpha4beta1 integrin, inhibits PIP formation. This study demonstrates the link between chemokine receptors and adhesion molecules that regulates stromal/hematopoietic cell interaction leading to PP formation.