title: T-helper cell-mediated proliferation and cytokine responses against recombinant Merkel cell polyomavirus-like particles.
abstract: The newly discovered Merkel Cell Polyomavirus (MCPyV) resides in approximately 80% of Merkel cell carcinomas (MCC). Causal role of MCPyV for this rare and aggressive skin cancer is suggested by monoclonal integration and truncation of large T (LT) viral antigen in MCC cells. The mutated MCPyV has recently been found in highly purified leukemic cells from patients with chronic lymphocytic leukemia (CLL), suggesting a pathogenic role also in CLL. About 50-80% of adults display MCPyV-specific antibodies. The humoral immunity does not protect against the development of MCC, as neutralizing MCPyV antibodies occur in higher levels among MCC patients than healthy controls. Impaired T-cell immunity has been linked with aggressive MCC behavior. Therefore, cellular immunity appears to be important in MCPyV infection surveillance. In order to elucidate the role of MCPyV-specific Th-cell immunity, peripheral blood mononuclear cells (PBMC) of healthy adults were stimulated with MCPyV VP1 virus-like particles (VLPs), using human bocavirus (HBoV) VLPs and Candida albicans antigen as positive controls. Proliferation, IFN-γ, IL-13 and IL-10 responses were examined in 15 MCPyV-seropositive and 15 seronegative volunteers. With the MCPyV antigen, significantly stronger Th-cell responses were found in MCPyV-seropositive than MCPyV-seronegative subjects, whereas with the control antigens, the responses were statistically similar. The most readily detectable cytokine was IFN-γ. The MCPyV antigen tended to induce stronger IFN-γ responses than HBoV VLP antigen. Taken together, MCPyV-specific Th-cells elicit vigorous IFN-γ responses. IFN-γ being a cytokine with major antiviral and tumor suppressing functions, Th-cells are suggested to be important mediators of MCPyV-specific immune surveillance.
authors: Departments of Virology, Haartman Institute, University of Helsinki, Helsinki, Finland. arun.kumar@helsinki.fi
authors: Arun
authors: A
authors: Kumar
authors: Tingting
authors: T
authors: Chen
authors: Sari
authors: S
authors: Pakkanen
authors: Anu
authors: A
authors: Kantele
authors: Maria
authors: M
authors: Söderlund-Venermo
authors: Klaus
authors: K
authors: Hedman
authors: Rauli
authors: R
authors: Franssila
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D002176:Candida albicans / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D056661:Human bocavirus / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D059965:Merkel cell polyomavirus / Q000276:immunology* / Q000648:ultrastructure; D008875:Middle Aged; D011995:Recombination, Genetic / Q000235:genetics*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology* / Q000821:virology; D014771:Virion / Q000276:immunology* / Q000648:ultrastructure
chemical_list: D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D016207:Cytokines; D006680:HLA Antigens; D018793:Interleukin-13; D016753:Interleukin-10; D007371:Interferon-gamma