It has been demonstrated that the two main subsets of peripheral γδ T cells, Vγ1 and Vγ4, have divergent functions in many diseases models. Recently, we reported that Vγ4 γδ T cells played a protective role in tumor immunity through eomesodermin-controlled mechanisms. However, the precise roles of Vγ1 γδ T cells in tumor immunity, especially whether Vγ1 γδ T cells have any interaction with Vγ4 γδ T cells, remain unknown. We demonstrated in this paper that Vγ1 γδ T cells suppressed Vγ4 γδ T cell-mediated antitumor function both in vitro and in vivo, and this suppression was cell contact independent. Using neutralizing anti–IL-4 Ab or IL-4−/− mice, we determined the suppressive factor derived from Vγ1 γδ T cells was IL-4. Indeed, treatment of Vγ4 γδ T cells with rIL-4 significantly reduced expression levels of NKG2D, perforin, and IFN-γ. Finally, Vγ1 γδ T cells produced more IL-4 and expressed significantly higher level of GATA-3 upon Th2 priming in comparison with Vγ4 γδ T cells. Therefore, to our knowledge, our results established for the first time a negative regulatory role of Vγ1 γδ T cells in Vγ4 γδ T cell-mediated antitumor immunity through cell contact-independent and IL-4–mediated mechanisms. Selective depletion of this suppressive subset of γδ T cells may be beneficial for tumor immune therapy.
This work was supported by grants from the National Outstanding Young Scientist Award of the National Natural Science Foundation of China (Grant 30725015) and the National Basic Research Program of China (Grant 2007CB914801) (to Z.Y.). It was also supported by the Program of Introducing Talents of Discipline to Universities (Grant B08011) and the Tianjin Municipal Science and Technology Commission (Grant 07ZCKFSH03600) (to Z.Y.). Z.H. was supported by the Tianjin Municipal Science and Technology Commission (Grant 09ZCKFSH08200). J. Han was supported by the National Basic Research Program of China (Grant 2010CB945003).
Abbreviations used in this article:
- airway hyperresponsiveness
- recombinant mouse
- Received May 12, 2011.
- Accepted September 2, 2011.
- Copyright © 2011 by The American Association of Immunologists, Inc.