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American Society of Hematology, Blood, 15(119), p. 3458-3468, 2012

DOI: 10.1182/blood-2011-09-378364

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MST1 mutations in autosomal recessive primary immunodeficiency characterized by defective naive T-cell survival

Journal article published in 2011 by Nadine T. Nehme, Nehme Nt, J. Pachlopnik Schmid ORCID, Jana Pachlopnik Schmid, Franck Debeurme, Isabelle André-Schmutz, Annick Lim, Patrick Nitschke, Frédéric Rieux-Laucat, Patrick Lutz, Capucine Picard ORCID, Nizar Mahlaoui, Alain Fischer, Geneviève de Saint Basile
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Abstract The molecular mechanisms that underlie T-cell quiescence are poorly understood. In the present study, we report a primary immunodeficiency phenotype associated with MST1 deficiency and primarily characterized by a progressive loss of naive T cells. The in vivo consequences include recurrent bacterial and viral infections and autoimmune manifestations. MST1-deficient T cells poorly expressed the transcription factor FOXO1, the IL-7 receptor, and BCL2. Conversely, FAS expression and the FAS-mediating apoptotic pathway were up-regulated. These abnormalities suggest that increased cell death of naive and proliferating T cells is the main mechanism underlying this novel immunodeficiency. Our results characterize a new mechanism in primary T-cell immunodeficiencies and highlight a role of the MST1/FOXO1 pathway in controlling the death of human naive T cells.