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RasGRP1 Regulates Antigen-Induced Developmental Programming by Naive CD8 T Cells
- Source :
- The Journal of Immunology. 184:666-676
- Publication Year :
- 2009
- Publisher :
- The American Association of Immunologists, 2009.
-
Abstract
- Ag encounter by naive CD8 T cells initiates a developmental program consisting of cellular proliferation, changes in gene expression, and the formation of effector and memory T cells. The strength and duration of TCR signaling are known to be important parameters regulating the differentiation of naive CD8 T cells, although the molecular signals arbitrating these processes remain poorly defined. The Ras-guanyl nucleotide exchange factor RasGRP1 has been shown to transduce TCR-mediated signals critically required for the maturation of developing thymocytes. To elucidate the role of RasGRP1 in CD8 T cell differentiation, in vitro and in vivo experiments were performed with 2C TCR transgenic CD8 T cells lacking RasGRP1. In this study, we report that RasGRP1 regulates the threshold of T cell activation and Ag-induced expansion, at least in part, through the regulation of IL-2 production. Moreover, RasGRP1−/− 2C CD8 T cells exhibit an anergic phenotype in response to cognate Ag stimulation that is partially reversible upon the addition of exogenous IL-2. By contrast, the capacity of IL-2/IL-2R interactions to mediate Ras activation and CD8 T cell expansion and differentiation appears to be largely RasGRP1-independent. Collectively, our results demonstrate that RasGRP1 plays a selective role in T cell signaling, controlling the initiation and duration of CD8 T cell immune responses.
- Subjects :
- T cell
Immunology
CD8-Positive T-Lymphocytes
Biology
Lymphocyte Activation
Jurkat cells
Mice
medicine
Animals
Guanine Nucleotide Exchange Factors
Immunology and Allergy
Cytotoxic T cell
Transgenes
IL-2 receptor
Antigens
Antigen-presenting cell
Cell Proliferation
Interleukin 3
Mice, Knockout
ZAP70
CD28
Cell Differentiation
Cell biology
medicine.anatomical_structure
Interleukin-2
Signal Transduction
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 184
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....1f8e0a646b73858375779b831d602f68