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

Michael A Curran ¹, Theresa L Geiger , Welby Montalvo , Myoungjoo Kim , Steven L Reiner , Aymen Al-Shamkhani , Joseph C Sun , James P Allison

Affiliations

¹ Department of Immunology, MD Anderson Cancer Center, Houston, TX 77030, USA.

PMID: 23547098
48 References
75 citations

Abstract

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.

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