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题目:
Primary MHC-class II(+) cells are necessary to promote resting Vδ2 cell expansion in response to (E)-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate and isopentenyl pyrophosphate.
作者:
Soriano-Sarabia(Natalia),Sandvold(Hakon),Jomaa(Hassan),Kubin(Thomas),Bein(Gregor),Hackstein(Holger)
状态:
发布时间2012-11-21 , 更新时间 2012-11-21
期刊:
J Immunol
摘要:
Human Vγ9δ2 (Vδ2) T cells represent a unique effector T cell population in humans and primates detecting nonpeptid phosphoantigens, playing an important role in antimicrobial and antitumor immunity. Currently, it is believed that various leukocyte subsets can promote phosphoantigen-driven Vδ2 cell expansion, but the essential cell type required remains elusive. We have used high purity cell sorting to analyze the cellular requirements for (E)-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate (HMBPP)-driven Vδ2 cell expansion. To our knowledge, we show for the first time that primary human MHC-class II(+) cells are indispensable for HMBPP- and isopentenylpyrophosphate-driven Vδ2 cell expansion. In contrast, MHC-class II(-) cells are unable to promote Vδ2 cell expansion. Moreover, purified primary human TCRαβ(+) T cells, CD4(+), or CD8(+) T cells also failed to promote HMBPP-mediated Vδ2 expansion. Depletion of CD4(+)CD25(+) T cells demonstrated that inability of TCRαβ(+) cells to expand Vδ2 cells was not related to the presence of regulatory T cells. Separation of MHC-class II(+) cells into dendritic cells, monocytes, and B cells revealed that dendritic cells were the most potent Vδ2 expanders. Pulsing experiments demonstrated that HMBPP transforms MHC-class II(+) but not negative cells into Vδ2 expanders. MHC-class II-blocking experiments with mAbs and secondary MHC-class II induction on CD4(+) T cells after CD3/CD28 costimulation indicated that MHC-class II is necessary, but not sufficient to promote Vδ2 expansion. Our results provide novel insight into the primary cell-specific requirements for human Vδ2 expansion.
语言:
eng
DOI:
10.4049/jimmunol.1200093

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