Virus stimulation of human mast cells results in the recruitment of CD56 + T cells by a mechanism dependent on CCR5 ligands
| Autor: | Sarah M. McAlpine, Jean S. Marshall, Thomas B. Issekutz |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Chemokine
Receptors CCR5 T-Lymphocytes Fluorescent Antibody Technique Ligands Biochemistry CCL5 03 medical and health sciences Interleukin 21 0302 clinical medicine Cell Movement Genetics Humans Cytotoxic T cell Mast Cells Chemokine CCL4 Chemokine CCL5 Mammalian orthoreovirus 3 Molecular Biology Cells Cultured Chemokine CCL3 030304 developmental biology 0303 health sciences Innate immune system Dose-Response Relationship Drug biology Chemistry Chemotaxis Fetal Blood Flow Cytometry CD56 Antigen 3. Good health Cell biology Interleukin 33 Culture Media Conditioned Host-Pathogen Interactions biology.protein Chemokines CD8 030215 immunology Biotechnology |
| Zdroj: | The FASEB Journal. 26:1280-1289 |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | The trafficking of effector cells to sites of infection is crucial for antiviral responses. However, the mechanisms of recruitment of the interferon-γ-producing and cytotoxic CD56(+) T cells are poorly understood. Human mast cells are sentinel cells found in the skin and airway and produce selected proinflammatory mediators in response to multiple pathogen-associated signals. The role of human mast cell-derived chemokines in T-cell recruitment to virus infection was examined. Supernatants from primary human cord blood-derived mast cells (CBMCs) infected with mammalian reovirus were examined for chemokine production and utilized in chemotaxis assays. Virus-infected CBMCs produced several chemokines, including CCL3, CCL4, and CCL5. Supernatants from reovirus-infected CBMCs selectively induced the chemotaxis of CD8(+) T cells (10±1%) and CD3(+)CD56(+) T cells (19±5%). CD56(+) T-cell migration was inhibited by pertussis toxin (65±9%) and met-RANTES (56±7%), a CCR1/CCR5 antagonist. CD56(+) T cells expressed CCR5, but little CCR1. The depletion of CCL3, CCL4, and CCL5 from reovirus-infected CBMC supernatants significantly (41±10%) inhibited CD56(+) T-cell chemotaxis. This study demonstrates a novel role for mast cells and CCR5 in CD56(+) T-cell trafficking and suggests that human mast cells enhance immunity to viruses through the selective recruitment of cytotoxic effector cells to virus infection sites. These findings could be exploited to enhance local T-cell responses in chronic viral infection and malignancies at mast cell-rich sites. |
| Databáze: | OpenAIRE |
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