CXCR3 chemokine receptor-ligand interactions in the lymph node optimize CD4+ T helper 1 cell differentiation

Immunity. 2012 Dec 14;37(6):1091-103. doi: 10.1016/j.immuni.2012.08.016. Epub 2012 Nov 1.


Differentiation of naive CD4(+) T cells into T helper (Th) cells is a defining event in adaptive immunity. The cytokines and transcription factors that control Th cell differentiation are understood, but it is not known how this process is orchestrated within lymph nodes (LNs). Here we have shown that the CXCR3 chemokine receptor was required for optimal generation of interferon-γ (IFN-γ)-secreting Th1 cells in vivo. By using a CXCR3 ligand reporter mouse, we found that stromal cells predominately expressed the chemokine ligand CXCL9 whereas hematopoietic cells expressed CXCL10 in LNs. Dendritic cell (DC)-derived CXCL10 facilitated T cell-DC interactions in LNs during T cell priming while both chemokines guided intranodal positioning of CD4(+) T cells to interfollicular and medullary zones. Thus, different chemokines acting on the same receptor can function locally to facilitate DC-T cell interactions and globally to influence intranodal positioning, and both functions contribute to Th1 cell differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology*
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / immunology
  • Chemokine CXCL9 / genetics
  • Chemokine CXCL9 / immunology
  • Chemokines, CXC / genetics
  • Chemokines, CXC / immunology
  • Cytokines / biosynthesis
  • DNA-Binding Proteins / genetics
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Gene Expression Regulation
  • Interferon-gamma / biosynthesis
  • Ligands
  • Lymph Nodes / immunology*
  • Lymph Nodes / metabolism*
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / metabolism
  • Mice
  • Mice, Transgenic
  • Protein Binding
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / metabolism*
  • Th1 Cells / cytology*
  • Th1 Cells / immunology*


  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines, CXC
  • Cytokines
  • DNA-Binding Proteins
  • Ligands
  • Receptors, CXCR3
  • Rex3 protein, mouse
  • Interferon-gamma