Title |
Role of γδ T Cells in α-Galactosylceramide–Mediated Immunity
|
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Published in |
The Journal of Immunology, April 2012
|
DOI | 10.4049/jimmunol.1103582 |
Pubmed ID | |
Authors |
Christophe Paget, Melvyn T. Chow, Helene Duret, Stephen R. Mattarollo, Mark J. Smyth |
Abstract |
Attempts to harness mouse type I NKT cells in different therapeutic settings including cancer, infection, and autoimmunity have proven fruitful using the CD1d-binding glycolipid α-galactosylceramide (α-GalCer). In these different models, the effects of α-GalCer mainly relied on the establishment of a type I NKT cell-dependent immune cascade involving dendritic cell, NK cell, B cell, or conventional CD4(+) and CD8(+) T cell activation/regulation as well as immunomodulatory cytokine production. In this study, we showed that γδ T cells, another population of innate-like T lymphocytes, displayed a phenotype of activated cells (cytokine production and cytotoxic properties) and were required to achieve an optimal α-GalCer-induced immune response. Using gene-targeted mice and recombinant cytokines, a critical need for IL-12 and IL-18 has been shown in the α-GalCer-induced IFN-γ production by γδ T cells. Moreover, this cytokine production occurred downstream of type I NKT cell response, suggesting their bystander effect on γδ T cells. In line with this, γδ T cells failed to directly recognize the CD1d/α-GalCer complex. We also provided evidence that γδ T cells increase their cytotoxic properties after α-GalCer injection, resulting in an increase in killing of tumor cell targets. Moreover, using cancer models, we demonstrated that γδ T cells were required for an optimal α-GalCer-mediated anti-tumor activity. Finally, we reported that immunization of wild-type mice with α-GalCer enhanced the adaptive immune response elicited by OVA, and this effect was strongly mediated by γδ T cells. We conclude that γδ T cells amplify the innate and acquired response to α-GalCer, with possibly important outcomes for the therapeutic effects of this compound. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 1 | 2% |
France | 1 | 2% |
Australia | 1 | 2% |
Unknown | 55 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 16 | 28% |
Researcher | 15 | 26% |
Student > Ph. D. Student | 7 | 12% |
Professor > Associate Professor | 4 | 7% |
Student > Doctoral Student | 3 | 5% |
Other | 7 | 12% |
Unknown | 6 | 10% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 27 | 47% |
Medicine and Dentistry | 9 | 16% |
Biochemistry, Genetics and Molecular Biology | 5 | 9% |
Chemistry | 3 | 5% |
Immunology and Microbiology | 3 | 5% |
Other | 5 | 9% |
Unknown | 6 | 10% |