title: Efficient generation and expansion of antigen-specific CD4+ T cells by recombinant influenza viruses.
abstract: Adoptive transfer of in vitro generated antigen-specific T cells has been successfully used to treat viral infections in immunodeficient patients. Therefore, methods for the rapid in vitro expansion of antigen-specific T cells are needed. Influenza virus efficiently infects dendritic cells, and peptides derived from viral proteins are processed and presented to CD8(+) cytotoxic T cells. However, both, CD4(+) and CD8(+) T cells are necessary for the efficient control of viral infections, and it is becoming increasingly clear that a T helper cell response is very important for the maintenance and strength of the immune response. Here we show that recombinant influenza virus efficiently infects a wide range of professional antigen-presenting cells and does not interfere with antigen presentation pathways. Using T cell clones for three different MHC class II-restricted antigens we demonstrate that peptides derived from these antigens are efficiently presented on MHC class II molecules. Importantly, it was possible to generate and expand antigen-specific CD4(+) T cells following in vitro infection of professional antigen-presenting cells with recombinant influenza virus. These findings support the notion that recombinant influenza virus is a valuable tool for the expansion of antigen-specific CD4(+) T cells in vitro.
authors.affiliation: Klinische Kooperationsgruppe, Pädiatrische Tumorimmunologie, Kinderklinik, Universitätsklinikum der Technischen Universität München, München, Germany. nimmerjahn@gsf.de
authors.forename: Falk
authors.initials: F
authors.lastname: Nimmerjahn
authors.forename: Dieter
authors.initials: D
authors.lastname: Kobelt
authors.forename: Alexander
authors.initials: A
authors.lastname: Steinkasserer
authors.forename: Annette
authors.initials: A
authors.lastname: Menke
authors.forename: Gerd
authors.initials: G
authors.lastname: Hobom
authors.forename: Uta
authors.initials: U
authors.lastname: Behrends
authors.forename: Georg W
authors.initials: GW
authors.lastname: Bornkamm
authors.forename: Josef
authors.initials: J
authors.lastname: Mautner
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002460:Cell Line; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D009975:Orthomyxoviridae / Q000276:immunology*; D011995:Recombination, Genetic; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II; C031540:M-protein, influenza virus; D014763:Viral Matrix Proteins