title: The Notch signaling pathway controls short-lived effector CD8+ T cell differentiation but is dispensable for memory generation.
abstract: Following an infection, naive CD8(+) T cells expand and differentiate into two main populations of effectors: short-lived effector cells (SLECs) and memory precursor effector cells (MPECs). There is limited understanding of the molecular mechanism and cellular processes governing this cell fate. Notch is a key regulator of cell fate decision relevant in many immunological pathways. In this study, we add to the role of Notch in cell fate decision and demonstrate that the Notch signaling pathway controls the MPEC/SLEC differentiation choice following both Listeria infection and dendritic cell immunization of mice. Although fewer SLECs were generated, Notch deficiency did not alter the rate of memory CD8(+) T cell generation. Moreover, we reveal that the Notch signaling pathway plays a context-dependent role for optimal cytokine production by effector CD8(+) T cells. Together, our results unravel critical functions for the Notch signaling pathway during effector CD8(+) T cell differentiation.
authors.affiliation: Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec H1T 2M4, Canada; Department of Microbiology, Infectiology and Immunology, University of Montreal, Montreal, Quebec H3T 1J4, Canada; and.
authors.forename: Mélissa
authors.initials: M
authors.lastname: Mathieu
authors.affiliation: Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec H1T 2M4, Canada; Department of Microbiology, Infectiology and Immunology, University of Montreal, Montreal, Quebec H3T 1J4, Canada; and.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Duval
authors.affiliation: Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec H1T 2M4, Canada;
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Daudelin
authors.affiliation: Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec H1T 2M4, Canada; Department of Microbiology, Infectiology and Immunology, University of Montreal, Montreal, Quebec H3T 1J4, Canada; and Department of Medicine, University of Montreal, Montreal, Quebec H3T 1J4, Canada nathalie.labrecque@umontreal.ca.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Labrecque
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D015870:Gene Expression; D007156:Immunologic Memory; D008087:Listeria / Q000276:immunology; D008088:Listeriosis / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D016207:Cytokines; D051880:Receptors, Notch; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor