Human airway epithelial cells present antigen to influenza virus-specific CD8+ CTL inefficiently after incubation with viral protein together with ISCOMATRIX.
In the present paper, an in vitro model was established in which the interaction between influenza virus-specific CD8+ T cells and human airway epithelial cells can be studied. To this end, the human lung epithelial cell line A549 was transduced with the HLA-A*0201 gene. This MHC class I allele is involved in the presentation of the immunodominant M158-66 cytotoxic T lymphocyte (CTL) epitope of the influenza A virus matrix protein. The A549-HLA-A2 cells and a CD8+ T cell clone specific for the M158-66 epitope were used to evaluate ISCOMATRIX (IMX), which is considered a potential mucosal adjuvant for influenza vaccines, for its capacity to activate virus-specific CTL after incubation with epithelial cells. It was found that virus infected epithelial cells activated virus-specific CTL efficiently. However, incubation of epithelial cells with ISCOMATRIX and recombinant M1 protein activated CD8+ T cells inefficiently, unlike the incubation of C1R cells expressing a HLA-A2 trans gene or HLA-A2+ B-lymphoblastoid cells with these reagents. It was concluded that this lack of antigen presentation by epithelial cells indicate that these cells are not subject to killing by virus-specific CTL upon instillation with ISCOMATRIX-based vaccines, which may be a favorable property of mucosal vaccines.
Rimmelzwaan
G F
GF
Institute of Virology, National Influenza Center, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. g.rimmelzwaan@erasmusmc.nl
Boon
A C M
AC
Geelhoed-Mieras
M M
MM
Voeten
J T M
JT
Fouchier
R A M
RA
Osterhaus
A D M E
AD
D000276:Adjuvants, Immunologic; D000938:Antigen-Presenting Cells / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002860:Chromium Radioisotopes; D004847:Epithelial Cells / Q000276:immunology*; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D009975:Orthomyxoviridae / Q000276:immunology*; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology; D012190:Retroviridae / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
D000276:Adjuvants, Immunologic; D002860:Chromium Radioisotopes; D015234:HLA-A Antigens; D014764:Viral Proteins; D007371:Interferon-gamma