Systemic 4-1BB activation induces a novel T cell phenotype driven by high expression of Eomesodermin

DOI PDF 被引用文献6件
  • Michael A. Curran
    Department of Immunology, MD Anderson Cancer Center, Houston, TX 77030 1
  • Theresa L. Geiger
    Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 2
  • Welby Montalvo
    Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 2
  • Myoungjoo Kim
    Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 2
  • Steven L. Reiner
    Department of Microbiology & Immunology 3 and 4
  • Aymen Al-Shamkhani
    Cancer Sciences Division University of Southampton School of Medicine, Southampton General Hospital, Southampton, Hampshire SO16 6YD, UK 5
  • Joseph C. Sun
    Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 2
  • James P. Allison
    Department of Immunology, MD Anderson Cancer Center, Houston, TX 77030 1

説明

<jats:p>4-1BB agonist antibody treatment induces a population of KLRG1+ T cells that infiltrate melanoma tumors. We investigated the origin and function of these cells, as well as their place within established T cell paradigms. We find that these T cells, particularly the CD4 lineage, represent a novel phenotype characterized by enhanced, multipotent cytotoxicity. Distinct from described polarities, this T cell phenotype is driven by the T-box transcription factor Eomesodermin. Formation of this phenotype requires 4-1BB signaling on both T and antigen-presenting cells and the resulting production of the cytokines IL-27, IL-15, and IL-10. Furthermore, we find CD4+ T cells bearing the signature features of this phenotype in the livers of mice infected with both bacterial and viral intracellular pathogens, suggesting a role for these cells in infectious immunity. These T cells constitute a novel phenotype that resolves multiple questions associated with 4-1BB activation, including how 4-1BB enhances tumor-specific cytotoxicity and how 4-1BB can promote tumor immunity while repressing autoimmunity.</jats:p>

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