Nanotubes Connect CD4+ T Cells to Airway Smooth Muscle Cells: Novel Mechanism of T Cell Survival
| Autor: | Saba Al Heialy, Paul-André Risse, Anne-Marie Lauzon, Toby K. McGovern, James G. Martin, Mauro Novali, Soroor Farahnak, Melissa A. Zeroual, Horia N. Roman |
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| Rok vydání: | 2015 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cell Survival T cell Cellular differentiation Myocytes Smooth Muscle Immunology Cell Apoptosis Cell Communication Respiratory Mucosa Biology Lymphocyte Activation Cell Adhesion medicine Humans Immunology and Allergy Cytotoxic T cell Calcium Signaling IL-2 receptor Cells Cultured CD40 Cell growth ZAP70 Antibodies Monoclonal Biological Transport respiratory system Coculture Techniques respiratory tract diseases Cell biology Hyaluronan Receptors medicine.anatomical_structure biology.protein Calcium |
| Zdroj: | The Journal of Immunology. 194:5626-5634 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1401718 |
| Popis: | Contact between airway smooth muscle (ASM) cells and activated CD4+ T cells, a key interaction in diseases such as asthma, triggers ASM cell proliferation and enhances T cell survival. We hypothesized that direct contact between ASM and CD4+ T cells facilitated the transfer of anti-apoptotic proteins via nanotubes, resulting in increased survival of activated CD4+ T cells. CD4+ T cells, isolated from PBMCs of healthy subjects, when activated and cocultured with ASM cells for 24 h, formed nanotubes that were visualized by immunofluorescence and atomic force microscopy. Cell-to-cell transfer of the fluorescent dye calcein-AM confirmed cytoplasmic communication via nanotubes. Immunoreactive B cell lymphoma 2 (Bcl-2) and induced myeloid leukemia cell differentiation protein (Mcl-1), two major anti-apoptotic proteins, were present within the nanotubes. Downregulation of Mcl-1 by small interfering RNA in ASM cells significantly increased T cell apoptosis, whereas downregulation of Bcl-2 had no effect. Transfer of GFP-tagged Mcl-1 from ASM cells to CD4+ T cells via the nanotubes confirmed directionality of transfer. In conclusion, activated T cells communicate with ASM cells via nanotube formation. Direct transfer of Mcl-1 from ASM to CD+ T cells via nanotubes is involved in T cell survival. This study provides a novel mechanism of survival of CD4+ T cells that is dependent on interaction with a structural cell. |
| Databáze: | OpenAIRE |
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