title: Mcl-1 regulates effector and memory CD8 T-cell differentiation during acute viral infection.
abstract: Mcl-1, an anti-apoptotic member of Bcl-2 family maintains cell viability during clonal expansion of CD8 T cells, but the cell intrinsic role of Mcl-1 in contraction of effectors or the number of memory CD8 T cells is unknown. Mcl-1 levels decline during the contraction phase but rebound to high levels in memory CD8 T cells. Therefore, by overexpressing Mcl-1 in CD8 T cells we asked whether limiting levels of Mcl-1 promote contraction of effectors and constrain CD8 T-cell memory. Mcl-1 overexpression failed to affect CD8 T-cell expansion, contraction or the magnitude of CD8 T-cell memory. Strikingly, high Mcl-1 levels enhanced mTOR phosphorylation and augmented the differentiation of terminal effector cells and effector memory CD8 T cells to the detriment of poly-cytokine-producing central memory CD8 T cells. Taken together, these findings provided unexpected insights into the role of Mcl-1 in the differentiation of effector and memory CD8 T cells.
authors: Department of Pathobiological Sciences, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA.
authors: Eui Ho
authors: EH
authors: Kim
authors: Department of Pathobiological Sciences, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA.
authors: Brandon
authors: B
authors: Neldner
authors: Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03755, USA.
authors: Jingang
authors: J
authors: Gui
authors: Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03755, USA.
authors: Ruth W
authors: RW
authors: Craig
authors: Department of Pathobiological Sciences, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA. Electronic address: sureshm@svm.vetmed.wisc.edu.
authors: M
authors: M
authors: Suresh
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation; D006801:Humans; D007156:Immunologic Memory; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000276:immunology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology
chemical_list: C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D058570:TOR Serine-Threonine Kinases
keywords: Apoptosis; Central memory; Differentiation; Effector; Effector memory; Lymphocytic choriomeningitis virus; Mammalian target of rapamycin; Memory; Myeloid cell leukemia 1