We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Chemokines enhance immunity by guiding naive CD8<sup>+</sup> T cells to sites of CD4<sup>+</sup> T cell–dendritic cell interaction.
- Authors
Castellino, Flora; Huang, Alex Y.; Altan-Bonnet, Grégoire; Stoll, Sabine; Scheinecker, Clemens; Germain, Ronald N.
- 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-1α and MIP-1β) 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.
- Subjects
T cells; PATHOGENIC microorganisms; LYMPH nodes; CANCER cells; IMMUNE response; CELL communication
- Publication
Nature, 2006, Vol 440, Issue 7086, p890
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature04651