title: Dissecting CD8+ NKT Cell Responses to Listeria Infection Reveals a Component of Innate Resistance.
abstract: A small pool of NK1.1(+) CD8(+) T cells is harbored among the conventional CD8(+) T cell compartment. Conclusions drawn from the analysis of immune responses mediated by cytotoxic CD8(+) T cells are often based on the total population, which includes these contaminating NK1.1(+) CD8(+) T cells. An unresolved question is whether NK1.1(+) CD8(+) cells are conventional T cells that acquire NK1.1 expression upon activation or delineation into memory phenotype or whether they are a distinct cell population that induces immune responses in a different manner than conventional T cells. To address this question, we used the Listeria monocytogenes model of infection and followed CD8(+) NK1.1(+) T cells and NK1.1(-) CD8(+) T cells during each phase of the immune response: innate, effector, and memory. Our central finding is that CD8(+) NK1.1(+) cells and conventional NK1.1(-) CD8(+) T cells both contribute to the adaptive immune response to Listeria, but only CD8(+) NK1.1(+) cells were equipped with the ability to provide a rapid innate immune response, as demonstrated by early and Ag-independent IFN-γ production, granzyme B expression, and degranulation. More importantly, purified conventional CD8(+) T cells alone, in the absence of any contaminating CD8(+) NK1.1(+) cells, were not sufficient to provide early protection to lethally infected mice. These results highlight the role of CD8(+) NK1.1(+) T cells in mounting early innate responses that are important for host defense and support the therapeutic potential of this subset to improve the effectiveness of protective immunity.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109; and.
authors.forename: Sergey S
authors.initials: SS
authors.lastname: Seregin
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109; and ylaouar@umich.edu.
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Laouar
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics; D053804:Granzymes / Q000096:biosynthesis; D007113:Immunity, Innate / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000235:genetics; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000637:transplantation
chemical_list: D000950:Antigens, Ly; C527211:Klrb1c protein, mouse; D055651:NK Cell Lectin-Like Receptor Subfamily B; D007371:Interferon-gamma; D053804:Granzymes; C509214:Gzmb protein, mouse