| First Author | Paget C | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 8 | Pages | 3928-39 |
| PubMed ID | 22412194 | Mgi Jnum | J:184074 |
| Mgi Id | MGI:5320228 | Doi | 10.4049/jimmunol.1103582 |
| Citation | Paget C, et al. (2012) Role of gammadelta T cells in alpha-galactosylceramide-mediated immunity. J Immunol 188(8):3928-39 |
| abstractText | 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 alpha-galactosylceramide (alpha-GalCer). In these different models, the effects of alpha-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 gammadelta 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 alpha-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 alpha-GalCer-induced IFN-gamma production by gammadelta T cells. Moreover, this cytokine production occurred downstream of type I NKT cell response, suggesting their bystander effect on gammadelta T cells. In line with this, gammadelta T cells failed to directly recognize the CD1d/alpha-GalCer complex. We also provided evidence that gammadelta T cells increase their cytotoxic properties after alpha-GalCer injection, resulting in an increase in killing of tumor cell targets. Moreover, using cancer models, we demonstrated that gammadelta T cells were required for an optimal alpha-GalCer-mediated anti-tumor activity. Finally, we reported that immunization of wild-type mice with alpha-GalCer enhanced the adaptive immune response elicited by OVA, and this effect was strongly mediated by gammadelta T cells. We conclude that gammadelta T cells amplify the innate and acquired response to alpha-GalCer, with possibly important outcomes for the therapeutic effects of this compound. |
