title: CXCR3 chemokine receptor-ligand interactions in the lymph node optimize CD4+ T helper 1 cell differentiation.
abstract: 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.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Joanna R
authors.initials: JR
authors.lastname: Groom
authors.forename: Jillian
authors.initials: J
authors.lastname: Richmond
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Murooka
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Sorensen
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Sung
authors.forename: Katherine
authors.initials: K
authors.lastname: Bankert
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
authors.forename: James J
authors.initials: JJ
authors.lastname: Moon
authors.forename: Thorsten R
authors.initials: TR
authors.lastname: Mempel
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology; D054370:Chemokine CXCL9 / Q000235:genetics / Q000276:immunology; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000096:biosynthesis; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology*
chemical_list: D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D016207:Cytokines; D004268:DNA-Binding Proteins; D008024:Ligands; D054367:Receptors, CXCR3; C116262:Rex3 protein, mouse; D007371:Interferon-gamma