title: 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.
abstract: 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.
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig University Giessen, Member of German Center for Lung Research, D-35390 Giessen, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Soriano-Sarabia
authors.forename: Hakon
authors.initials: H
authors.lastname: Sandvold
authors.forename: Hassan
authors.initials: H
authors.lastname: Jomaa
authors.forename: Thomas
authors.initials: T
authors.lastname: Kubin
authors.forename: Gregor
authors.initials: G
authors.lastname: Bein
authors.forename: Holger
authors.initials: H
authors.lastname: Hackstein
mesh_terms: D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D011756:Diphosphates / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D045782:Hemiterpenes / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D061251:Primary Cell Culture; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
chemical_list: C443995:4-hydroxy-3-methylbut-2-enyl pyrophosphate; D000906:Antibodies; D015703:Antigens, CD; D011756:Diphosphates; D045782:Hemiterpenes; D000949:Histocompatibility Antigens Class II; D007155:Immunologic Factors; D009943:Organophosphorus Compounds; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C521523:T-cell receptor Vdelta2, human; C004809:isopentenyl pyrophosphate