Chemokines Enhance Immunity by Guiding Naive CD8+ T Cells to Sites of CD4+ T Cell-Dendritic Cell Interaction

Nature. 2006 Apr 13;440(7086):890-5. doi: 10.1038/nature04651.

Abstract

CD8+ T cells have a crucial role in resistance to pathogens and can kill malignant cells; however, some critical functions of these lymphocytes depend on helper activity provided by a distinct population of CD4+ T cells. Cooperation between these lymphocyte subsets involves recognition of antigens co-presented by the same dendritic cell, but the frequencies of such antigen-bearing cells early in an infection and of the relevant naive T cells are both low. This suggests that an active mechanism facilitates the necessary cell-cell associations. Here we demonstrate that after immunization but before antigen recognition, naive CD8+ T cells in immunogen-draining lymph nodes upregulate the chemokine receptor CCR5, permitting these cells to be attracted to sites of antigen-specific dendritic cell-CD4+ T cell interaction where the cognate chemokines CCL3 and CCL4 (also known as MIP-1alpha and MIP-1beta) are produced. Interference with this actively guided recruitment markedly reduces the ability of CD4+ T cells to promote memory CD8+ T-cell generation, indicating that an orchestrated series of differentiation events drives nonrandom cell-cell interactions within lymph nodes, optimizing CD8+ T-cell immune responses involving the few antigen-specific precursors present in the naive repertoire.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Adhesion
  • Cell Communication*
  • Cell Movement
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokines / antagonists & inhibitors
  • Chemokines / immunology*
  • Chemokines / metabolism
  • Chemokines, CC / immunology
  • Chemokines, CC / metabolism
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology
  • Immunologic Memory / immunology
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymphocyte Activation
  • Macrophage Inflammatory Proteins / immunology
  • Macrophage Inflammatory Proteins / metabolism
  • Mice
  • Receptors, CCR5 / immunology
  • Receptors, CCR5 / metabolism

Substances

  • Ccl3 protein, mouse
  • Ccl4 protein, mouse
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokines
  • Chemokines, CC
  • Macrophage Inflammatory Proteins
  • Receptors, CCR5