TY - JOUR
T1 - Systemic 4-1BB activation induces a novel T cell phenotype driven by high expression of eomesodermin
AU - Curran, Michael A.
AU - Geiger, Theresa L.
AU - Montalvo, Welby
AU - Kim, Myoungjoo
AU - Reiner, Steven L.
AU - Al-Shamkhani, Aymen
AU - Sun, Joseph C.
AU - Allison, James P.
PY - 2013
Y1 - 2013
N2 - 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 antigenpresenting 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.
AB - 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 antigenpresenting 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.
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U2 - 10.1084/jem.20121190
DO - 10.1084/jem.20121190
M3 - Article
C2 - 23547098
AN - SCOPUS:84878648242
SN - 0022-1007
VL - 210
SP - 743
EP - 755
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 4
ER -