Pathogen-Induced Inflammatory Environment Controls Effector and Memory CD8+ T Cell Differentiation

  • Joshua J. Obar
    *Center for Integrated Immunology and Vaccine Research, Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030; and
  • Evan R. Jellison
    *Center for Integrated Immunology and Vaccine Research, Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030; and
  • Brian S. Sheridan
    *Center for Integrated Immunology and Vaccine Research, Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030; and
  • David A. Blair
    *Center for Integrated Immunology and Vaccine Research, Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030; and
  • Quynh-Mai Pham
    *Center for Integrated Immunology and Vaccine Research, Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030; and
  • Julianne M. Zickovich
    †Department of Immunology and Infectious Diseases, Montana State University, Bozeman, MT 59718
  • Leo Lefrançois
    *Center for Integrated Immunology and Vaccine Research, Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030; and

抄録

<jats:title>Abstract</jats:title> <jats:p>In response to infection, CD8+ T cells integrate multiple signals and undergo an exponential increase in cell numbers. Simultaneously, a dynamic differentiation process occurs, resulting in the formation of short-lived effector cells (SLECs; CD127lowKLRG1high) and memory precursor effector cells (CD127highKLRG1low) from an early effector cell that is CD127lowKLRG1low in phenotype. CD8+ T cell differentiation during vesicular stomatitis virus infection differed significantly than during Listeria monocytogenes infection with a substantial reduction in early effector cell differentiation into SLECs. SLEC generation was dependent on Ebi3 expression. Furthermore, SLEC differentiation during vesicular stomatitis virus infection was enhanced by administration of CpG-DNA, through an IL-12–dependent mechanism. Moreover, CpG-DNA treatment enhanced effector CD8+ T cell functionality and memory subset distribution, but in an IL-12–independent manner. Population dynamics were dramatically different during secondary CD8+ T cell responses, with a much greater accumulation of SLECs and the appearance of a significant number of CD127highKLRG1high memory cells, both of which were intrinsic to the memory CD8+ T cell. These subsets persisted for several months but were less effective in recall than memory precursor effector cells. Thus, our data shed light on how varying the context of T cell priming alters downstream effector and memory CD8+ T cell differentiation.</jats:p>

収録刊行物

  • The Journal of Immunology

    The Journal of Immunology 187 (10), 4967-4978, 2011-11-15

    The American Association of Immunologists

被引用文献 (5)*注記

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