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CD134 plus CD137 dual costimulation induces Eomesodermin in CD4 T cells to program cytotoxic Th1 differentiation.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2011 Oct 01; Vol. 187 (7), pp. 3555-64. Date of Electronic Publication: 2011 Aug 31. - Publication Year :
- 2011
-
Abstract
- Cytotoxic CD4 Th1 cells are emerging as a therapeutically useful T cell lineage that can effectively target tumors, but until now the pathways that govern their differentiation have been poorly understood. We demonstrate that CD134 (OX40) costimulation programs naive self- and virus-reactive CD4 T cells to undergo in vivo differentiation into cytotoxic Th1 effectors. CD137 (4-1BB) costimulation maximized clonal expansion, and IL-2 was necessary for cytotoxic Th1 differentiation. Importantly, the T-box transcription factor Eomesodermin was critical for inducing the cytotoxic marker granzyme B. CD134 plus CD137 dual costimulation also imprinted a cytotoxic phenotype on bystanding CD4 T cells. Thus, to our knowledge, the current study identifies for the first time a specific costimulatory pathway and an intracellular mechanism relying on Eomesodermin that induces both Ag-specific and bystander cytotoxic CD4 Th1 cells. This mechanism might be therapeutically useful because CD134 plus CD137 dual costimulation induced CD4 T cell-dependent tumoricidal function in a mouse melanoma model.
- Subjects :
- Animals
CD4-Positive T-Lymphocytes cytology
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes metabolism
Cell Separation
Chromatin Immunoprecipitation
Flow Cytometry
Melanoma, Experimental immunology
Mice
Mice, Transgenic
Receptors, OX40 metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction immunology
T-Box Domain Proteins metabolism
Th1 Cells immunology
Th1 Cells metabolism
Tumor Necrosis Factor Receptor Superfamily, Member 9 metabolism
Cell Differentiation immunology
Receptors, OX40 immunology
T-Box Domain Proteins immunology
Th1 Cells cytology
Tumor Necrosis Factor Receptor Superfamily, Member 9 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 187
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 21880986
- Full Text :
- https://doi.org/10.4049/jimmunol.1101244