Systemic 4-1BB activation induces a novel T cell phenotype driven by high expression of eomesodermin Journal Article
| Authors: | Curran, M. A.; Geiger, T. L.; Montalvo, W.; Kim, M.; Reiner, S. L.; Al Shamkhani, A.; Sun, J. C.; Allison, J. P. |
| Article Title: | Systemic 4-1BB activation induces a novel T cell phenotype driven by high expression of eomesodermin |
| 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 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. © 2013 Curran et al. |
| Keywords: | genetics; drug potentiation; mouse; animal; cytology; metabolism; mouse mutant; animals; mice; mice, knockout; melanoma; pathology; physiology; gene expression regulation; cytokine; biosynthesis; immunology; cytokines; cd4+ t lymphocyte; cd4-positive t-lymphocytes; autoimmunity; receptors, immunologic; t box transcription factor; immunoglobulin receptor; cd137 antigen; antigens, cd137; t-box domain proteins; eomes protein, mouse; klrg1 protein, mouse |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 210 |
| Issue: | 4 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2013-04-08 |
| Start Page: | 743 |
| End Page: | 755 |
| Language: | English |
| DOI: | 10.1084/jem.20121190 |
| PUBMED: | 23547098 |
| PROVIDER: | scopus |
| PMCID: | PMC3620352 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 July 2013" - "CODEN: JEMEA" - "Source: Scopus" |
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