Nanotubes connect CD4+ T cells to airway smooth muscle cells: novel mechanism of T cell survival.
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.
Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec H2X 2P2, Canada; andResearch Institute, McGill University Health Centre, Montreal, Quebec H2X 2P2, Canada.
Saba
S
Al Heialy
Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec H2X 2P2, Canada; andResearch Institute, McGill University Health Centre, Montreal, Quebec H2X 2P2, Canada.
Melissa
M
Zeroual
Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec H2X 2P2, Canada; andResearch Institute, McGill University Health Centre, Montreal, Quebec H2X 2P2, Canada.
Soroor
S
Farahnak
Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec H2X 2P2, Canada; andResearch Institute, McGill University Health Centre, Montreal, Quebec H2X 2P2, Canada.
Toby
T
McGovern
Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec H2X 2P2, Canada; andResearch Institute, McGill University Health Centre, Montreal, Quebec H2X 2P2, Canada.
Paul-André
PA
Risse
Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec H2X 2P2, Canada; andResearch Institute, McGill University Health Centre, Montreal, Quebec H2X 2P2, Canada.
Mauro
M
Novali
Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec H2X 2P2, Canada; andResearch Institute, McGill University Health Centre, Montreal, Quebec H2X 2P2, Canada.
Anne-Marie
AM
Lauzon
Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec H2X 2P2, Canada; andResearch Institute, McGill University Health Centre, Montreal, Quebec H2X 2P2, Canada.
Horia N
HN
Roman
Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec H2X 2P2, Canada; andResearch Institute, McGill University Health Centre, Montreal, Quebec H2X 2P2, Canada james.martin@mcgill.ca.
James G
JG
Martin
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001692:Biological Transport; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors; D002118:Calcium