title: Transfer of CD8+ T cell memory using Bcl-2 as a marker.
abstract: The processes that regulate T cell memory generation are important for therapeutic design and the immune response to disease. However, what allows a subset of effector T cells to survive the contraction period to become memory cells is incompletely understood. The Bcl-2 family is critical for T cell survival, and Bcl-2 has been proposed to be important for the survival of memory cells. However, previous studies have relied on double-knockout models, potentially skewing the role of Bcl-2, and the use of Bcl-2 as a marker in adoptive transfer experiments, a method required to confirm the memory potential of cell subsets, has not been possible because of the intracellular localization of the protein. In this study, we present a novel Bcl-2 reporter mouse model and, to our knowledge, show for the first time that a distinct subset of effector T cells, and also a subset within the CD127(hi)KLRG1(lo) memory precursor effector cell population, retains high Bcl-2 expression at the peak of the CD8(+) T cell response to Listeria monocytogenes. Furthermore, we show that Bcl-2 correlates with memory potential in adoptive transfer experiments using both total responding CD8(+) T cells and memory precursor effector cells. These results show that even within the memory precursor effector cell population, Bcl-2 confers a survival advantage in a subset of effector CD8(+) T cells that allows differentiation into memory cells and cement Bcl-2 as a critical factor for T cell memory.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Dunkle
authors.forename: Ivan
authors.initials: I
authors.lastname: Dzhagalov
authors.forename: Claire
authors.initials: C
authors.lastname: Gordy
authors.forename: You-Wen
authors.initials: YW
authors.lastname: He
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D022202:Chromosomes, Artificial, Bacterial; D017930:Genes, Reporter; D019254:Genes, bcl-2; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008164:Luminescent Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D019076:Transgenes
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; C054562:yellow fluorescent protein, Bacteria; D010047:Ovalbumin