| First Author | Gruenbacher G | Year | 2016 |
| Journal | Cell Rep | Volume | 16 |
| Issue | 2 | Pages | 444-56 |
| PubMed ID | 27346340 | Mgi Jnum | J:238523 |
| Mgi Id | MGI:5822971 | Doi | 10.1016/j.celrep.2016.06.009 |
| Citation | Gruenbacher G, et al. (2016) Ecto-ATPase CD39 Inactivates Isoprenoid-Derived Vgamma9Vdelta2 T Cell Phosphoantigens. Cell Rep 16(2):444-56 |
| abstractText | In humans, Vgamma9Vdelta2 T cells respond to self and pathogen-associated, diphosphate-containing isoprenoids, also known as phosphoantigens (pAgs). However, activation and homeostasis of Vgamma9Vdelta2 T cells remain incompletely understood. Here, we show that pAgs induced expression of the ecto-ATPase CD39, which, however, not only hydrolyzed ATP but also abrogated the gammadelta T cell receptor (TCR) agonistic activity of self and microbial pAgs (C5 to C15). Only mevalonate-derived geranylgeranyl diphosphate (GGPP, C20) resisted CD39-mediated hydrolysis and acted as a regulator of CD39 expression and activity. GGPP enhanced macrophage differentiation in response to the tissue stress cytokine interleukin-15. In addition, GGPP-imprinted macrophage-like cells displayed increased capacity to produce IL-1beta as well as the chemokine CCL2 and preferentially activated CD161-expressing CD4(+) T cells in an innate-like manner. Our studies reveal a previously unrecognized immunoregulatory function of CD39 and highlight a particular role of GGPP among pAgs. |
