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

Curran, M.A., Geiger, T.L., Montalvo, W., Kim, M., Reiner, S.L., Al-Shamkhani, Aymen, Sun, J.C. and Allison, J.P. (2013) Systemic 4-1BB activation induces a novel T cell phenotype driven by high expression of Eomesodermin. Journal of Experimental Medicine, 210 (4), 743-755. (doi:10.1084/jem.20121190). (PMID:23547098)

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.

This record has no associated files available for download.

Contributors

Author: Aymen Al-Shamkhani

Download statistics