CD4+CD3- cells induce Peyer's patch development: role of alpha4beta1 integrin activation by CXCR5

Immunity. 2002 Sep;17(3):363-73. doi: 10.1016/s1074-7613(02)00395-3.


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 PP, we studied mice deficient in CXCR5 and/or alpha4beta1 integrin-mediated adhesion. CXCR5-/- mice have CD4+CD3- cells, which are inefficient in inducing PP 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 PP formation. This study demonstrates the link between chemokine receptors and adhesion molecules that regulates stromal/hematopoietic cell interaction leading to PP formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD3 Complex / analysis
  • CD4-Positive T-Lymphocytes / physiology*
  • CD4-Positive T-Lymphocytes / transplantation
  • Cell Adhesion
  • Chemokine CXCL13
  • Chemokines, CXC / physiology
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / immunology
  • Integrin alpha4beta1 / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Immunological
  • Morphogenesis
  • Peyer's Patches / growth & development*
  • Radiation Chimera
  • Receptors, CXCR5
  • Receptors, Chemokine
  • Receptors, Cytokine / deficiency
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / physiology*
  • Signal Transduction / immunology
  • Stromal Cells / cytology
  • Vascular Cell Adhesion Molecule-1 / physiology


  • CD3 Complex
  • CXCR5 protein, mouse
  • Chemokine CXCL13
  • Chemokines, CXC
  • Cxcl13 protein, mouse
  • Integrin alpha4beta1
  • Receptors, CXCR5
  • Receptors, Chemokine
  • Receptors, Cytokine
  • Vascular Cell Adhesion Molecule-1