title: Regulatory role of Vγ1 γδ T cells in tumor immunity through IL-4 production.
abstract: 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.
authors: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors: Jianlei
authors: J
authors: Hao
authors: Siyuan
authors: S
authors: Dong
authors: Siyuan
authors: S
authors: Xia
authors: Weifeng
authors: W
authors: He
authors: Hao
authors: H
authors: Jia
authors: Song
authors: S
authors: Zhang
authors: Jun
authors: J
authors: Wei
authors: Rebecca L
authors: RL
authors: O'Brien
authors: Willi K
authors: WK
authors: Born
authors: Zhenzhou
authors: Z
authors: Wu
authors: Puyue
authors: P
authors: Wang
authors: Jihong
authors: J
authors: Han
authors: Zhangyong
authors: Z
authors: Hong
authors: Liqing
authors: L
authors: Zhao
authors: Zhinan
authors: Z
authors: Yin
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology*
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta; D015847:Interleukin-4