CXCR3 Chemokine Receptor-ligand Interactions in the Lymph Node Optimize CD4+ T Helper 1 Cell Differentiation

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2012 Nov 6

PMID 23123063

Citations 232

Authors

Joanna R Groom

Jillian Richmond

Thomas T Murooka

Elizabeth W Sorensen

Jung Hwan Sung

Katherine Bankert

Ulrich H von Andrian

James J Moon

Thorsten R Mempel

Andrew D Luster

Affiliations

Soon will be listed here.

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.

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