The lymphoid chemokine CCL21 costimulates naive T cell expansion and Th1 polarization of non-regulatory CD4+ T cells

Cell Immunol. Sep-Oct 2004;231(1-2):75-84. doi: 10.1016/j.cellimm.2004.12.006. Epub 2005 Jan 21.

Abstract

CCL21 (SLC/6Ckine) is constitutively expressed by secondary lymphoid tissue and attracts CCR7-expressing mature dendritic cells and naive T cells. Recent studies demonstrated that intra-tumoral delivery of CCL21 induces tumor regression in a T cell dependent manner. CCL21 is known to mediate T cell trafficking but little is known about its function as a costimulatory molecule. Herein, we demonstrate that CCL21 costimulates expansion of CD4+ and CD8+ T cells and induces Th1 polarization. These effects were specific for naive T cells, and we show that CD4+CD25+ regulatory T cells were hyporesponsive to CCL21 induced migration, and unresponsive to CCL21 costimulation. These unique functions of CCL21 to both attract naive T cells as well as costimulate their proliferation and differentiation, suggests that CCL21 is a pivotal molecule for priming T cell responses and has therapeutic implications for local delivery of CCL21. The coordinated effects of CCL21 on T cell migration and activation may also represent a more comprehensive paradigm for the activity of other chemokines as well.

Publication types

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

MeSH terms

  • Animals
  • CD4 Antigens / immunology
  • Cell Polarity / drug effects*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chemokine CCL21
  • Chemokines, CC / pharmacology*
  • Cytokines / metabolism
  • Female
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lymphocyte Activation / immunology
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Mice
  • Protein Binding
  • Receptors, Interleukin-2 / immunology
  • Substrate Specificity
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Th1 Cells / cytology*
  • Th1 Cells / drug effects*

Substances

  • CD4 Antigens
  • Ccl21c protein, mouse
  • Chemokine CCL21
  • Chemokines, CC
  • Cytokines
  • Lymphocyte Function-Associated Antigen-1
  • Receptors, Interleukin-2
  • Intercellular Adhesion Molecule-1