HUMAN MESENCHYMAL STEM CELLS PROMOTE SURVIVAL OF T CELLS IN A QUIESCENT STATE

¹ Neuroimmunology Unit, Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Italy; Centre of Excellence for Biomedical Research, University of Genoa, Italy
² Neuroimmunology Unit, Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Italy
³ Department of Haematology, San Martino Hospital, Genoa, Italy
⁴ Laboratory of Oncology, IRCCS G. Gaslini, Genova, Italy

^* To whom correspondence should be addressed. E-mail: auccelli{at}neurologia.unige.it.

	Abstract

Mesenchymal stem cells (MSC) are part of the bone marrow where they provide signals supporting survival and growth of bystander haematopoietic 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 condition. 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.

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