title: Influenza virosomes enhance class I restricted CTL induction through CD4+ T cell activation.
abstract: Immunopotentiating reconstituted influenza virosomes (IRIV) are one of the few adjuvants currently licensed for human use. While their adjuvant capacity in the induction of humoral responses is clearly documented, few data exist on their effects on T cell immune response. Here we addressed IRIV adjuvance in the induction of HLA class I restricted cytotoxic T lymphocytes (CTL) in vitro. Lymphocyte stimulation with IM(58-66) and IRIV resulted in marked expansion of specific CTL as compared to cultures performed in the presence of either antigen alone or antigen and control liposomes (L). Studies addressing underlying adjuvant mechanisms demonstrated that IRIV activated CD4/CD45RO+ T cells, induced a cytokine profile consistent with T helper 1 (Th1) stimulation and increased the percentage of CD4+ T cells expressing CXCR3. Furthermore, supernatants from IRIV stimulated PBMC cultures promoted dendritic cell maturation. Most importantly, IRIV mediated CTL adjuvance required the presence of live CD4+ T cells. Powerful adjuvant effects of IRIV were also observed in the induction of CTL specific for the melanoma associated Melan-A/MART-1(27-35), HLA-A0201 restricted epitope. Taken together these findings indicate that IRIV are endowed with a high adjuvant capacity for HLA class I restricted CTL induction, largely attributable to their ability to antigenically stimulate CD4+ T cells.
authors.affiliation: Department of Surgery, University of Basel, Basel, Switzerland.
authors.forename: Reto
authors.initials: R
authors.lastname: Schumacher
authors.forename: Michel
authors.initials: M
authors.lastname: Adamina
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Zurbriggen
authors.forename: Martin
authors.initials: M
authors.lastname: Bolli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Padovan
authors.forename: Paul
authors.initials: P
authors.lastname: Zajac
authors.forename: Michael
authors.initials: M
authors.lastname: Heberer
authors.forename: Giulio C
authors.initials: GC
authors.lastname: Spagnoli
mesh_terms: D000276:Adjuvants, Immunologic; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D000939:Epitopes / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D005805:Genes, MHC Class I / Q000235:genetics; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D008081:Liposomes; D008213:Lymphocyte Activation / Q000502:physiology*; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology; D022701:Virosomes / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000939:Epitopes; D007252:Influenza Vaccines; D008081:Liposomes; D014764:Viral Proteins; D022701:Virosomes