Human mesenchymal stem cells promote survival of T cells in a quiescent state.
Mesenchymal stem cells (MSC) are part of the bone marrow that provides signals supporting survival and growth of bystander hematopoietic stem cells (HSC). MSC modulate also the immune response, as they inhibit proliferation of lymphocytes. In order to investigate whether MSC can support survival of T cells, we investigated MSC capacity of rescuing T lymphocytes from cell death induced by different mechanisms. We observed that MSC prolong survival of unstimulated T cells and apoptosis-prone thymocytes cultured under starving conditions. MSC rescued T cells from activation induced cell death (AICD) by downregulation of Fas receptor and Fas ligand on T cell surface and inhibition of endogenous proteases involved in cell death. MSC dampened also Fas receptor mediated apoptosis of CD95 expressing Jurkat leukemic T cells. In contrast, rescue from AICD was not associated with a significant change of Bcl-2, an inhibitor of apoptosis induced by cell stress. Accordingly, MSC exhibited a minimal capacity of rescuing Jurkat cells from chemically induced apoptosis, a process disrupting the mitochondrial membrane potential regulated by Bcl-2. These results suggest that MSC interfere with the Fas receptor regulated process of programmed cell death. Overall, MSC can inhibit proliferation of activated T cells while supporting their survival in a quiescent state, providing a model of their activity inside the HSC niche. Disclosure of potential conflicts of interest is found at the end of this article.
Benvenuto
Federica
F
Neuroimmunology Unit, Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Via De Toni 5, 16132 Genoa, Italy.
Ferrari
Stefania
S
Gerdoni
Ezio
E
Gualandi
Francesca
F
Frassoni
Francesco
F
Pistoia
Vito
V
Mancardi
Gianluigi
G
Uccelli
Antonio
A
D017209:Apoptosis; D002455:Cell Division; D002470:Cell Survival; D002648:Child; D015536:Down-Regulation / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010447:Peptide Hydrolases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D053218:Receptors, Death Domain / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology*; D019014:fas Receptor / Q000378:metabolism
C491901:FAS protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D053218:Receptors, Death Domain; D019014:fas Receptor; D010447:Peptide Hydrolases