Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse
| Autor: | Christina K. Chan, Brian Kinsella, Rebecca P. Wu, Stephen P. Evanko, Paul L. Bollyky, Thomas N. Wight, Brandon Teng, Helena Reijonen, Kathy R. Braun, John A. Gebe, Kelly Guebtner, Gerald T. Nepom, S. Alice Long, Susan Potter-Perigo |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
T-Lymphocytes
T cell Immunology Antigen presentation Biology Immunological synapse Cell Adhesion medicine Humans Immunology and Allergy Interferon gamma Hyaluronic Acid Antigen-presenting cell Cell Shape Cells Cultured Dendritic Cells Dendritic cell Th1 Cells Cell biology Infectious Diseases medicine.anatomical_structure Cytokines Cytokine secretion Tumor necrosis factor alpha Research Article medicine.drug |
| Zdroj: | Cellular & Molecular Immunology. 7:211-220 |
| ISSN: | 2042-0226 1672-7681 |
| DOI: | 10.1038/cmi.2010.9 |
| Popis: | Hyaluronan (HA) production by dendritic cells (DCs) is known to promote antigen presentation and to augment T-cell activation and proliferation. We hypothesized that pericellular HA can function as intercellular 'glue' directly mediating T cell-DC binding. Using primary human cells, we observed HA-dependent binding between T cells and DCs, which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone (4-MU), an agent which blocks HA synthesis. Furthermore, T cells regulate HA production by DCs via T cell-derived cytokines in a T helper (Th) subset-specific manner, as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production. Similar effects were seen upon the addition of exogenous Th1 cytokines, IL-2, interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). The critical factors which determined the extent of DC-T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA, as T-cell clones which were pre-treated with monensin, added to block cytokine secretion, bound equivalently irrespective of their Th subset. These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA, which in turn affects the extent of DC-T cell binding. We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation. These data point to a pivotal role for HA in DC-T cell interactions at the IS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|