title: Novel immunostimulatory effects of osteoclasts and macrophages on human γδ T cells.
abstract: It has been widely reported that T cells are capable of influencing osteoclast formation and bone remodelling, yet relatively little is known of the reciprocal effects of osteoclasts for affecting T cell function and/or activity. In this study we investigated the effects of human osteoclasts on the function of γδ T cells, a subset of non-CD4(+) T cells implicated in a variety of inflammatory disease states. γδ T cells and CD4(+) T cells were isolated from peripheral blood of healthy volunteers and were co-cultured with autologous mature osteoclasts (generated by treatment with M-CSF and RANKL) before phenotypical and functional changes in the T cell populations were assessed. Macrophages, osteoclasts, and conditioned medium derived from macrophages or osteoclasts induced activation of γδ T cells, as determined by the expression of the early activation marker CD69. TNFα was a major mediator of this stimulatory effect on γδ T cells. Consistent with this stimulatory effect, osteoclasts augmented proliferation of IL-2-stimulated γδ T cells and also supported the survival of unstimulated γδ and CD4(+) T cells, although these effects required co-culture with osteoclasts. Co-culture with osteoclasts also increased the proportion of γδ T cells producing IFNγ, but did not modulate IFNγ or IL-17 production by CD4(+) T cells. We provide new insights into the in vitro interactions between human γδ T cells and osteoclasts/macrophages, and demonstrate that osteoclasts or their precursors are capable of influencing γδ T function both via the release of soluble factors and also through direct cell-cell interactions.
authors.affiliation: Musculoskeletal Research Programme, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Pappalardo
authors.affiliation: Musculoskeletal Research Programme, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK. Electronic address: k.thompson@abdn.ac.uk.
authors.forename: Keith
authors.initials: K
authors.lastname: Thompson
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis; D002633:Chemotaxis / Q000187:drug effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D037181:Lectins, C-Type / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018925:Chemokines; D017077:Culture Media, Conditioned; D037181:Lectins, C-Type; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens
keywords: CD69; Chemotaxis; IFNγ; Osteoclast; TNFα; γδ T cell