title: CIITA-driven MHC class II expressing tumor cells can efficiently prime naive CD4+TH cellsin vivoand vaccinate the host against parental MHC-II-negative tumor cells.
abstract: Our previous studies showed that non-immunogenic H-2dtumor cells of distinct epithelial histotypes can become highly immunogenic, induce a protective CD4+T cell response and vaccinate the animals against parental MHC-II-negative cells if they are rendered MHC class II-positive by stable transfection with the Air-1-encoded MHC-II transcriptional activator CIITA. These studies did not establish, however, whether tumor immunity was the consequence of a direct priming of naive CD4+T lymphocytes by CIITA-driven MHC-II-expressing tumor cells or by MHC-II-tumor antigen complexes engulfed by dendritic cells (DC) and exposed on the surface of these professional antigen presenting cells (APC). In the present investigation, we provide definitive evidence that CIITA-tumor cells are the crucial APCin vivofor CD4+T cell priming. By using a transgenic H-2bmouse model, the CD11c.DTR C57BL/6 mice, in which DC can be functionally deleted by administration of diphteria toxin, we show that CIITA-tumor cells of two distinct histotypes can be rejected or strongly retarded in their growth in DC-deleted mice. To rule out that in absence of DC, other professional APC could prime naive CD4+T cells, we deleted the macrophages in CD11c.DTR C57BL/6 mice by administration of liposome Clodronate and still obtained rejection or strong retardation in tumor growth of CIITA-tumor cells. Our results challenge the diffuse belief that non-professional APC cannot efficiently prime naive T cellsin vivo.Moreover, the demonstration of the general validity of our approach in different genetic backgrounds may open a way for new strategies of antitumor treatment in clinical settings.
authors.affiliation: Department of Surgical and Morphological Sciences, School of Medicine, University of Insubria , Varese, Italy.
authors.forename: Farah
authors.initials: F
authors.lastname: Bou Nasser Eddine
authors.affiliation: Department of Surgical and Morphological Sciences, School of Medicine, University of Insubria , Varese, Italy.
authors.forename: Greta
authors.initials: G
authors.lastname: Forlani
authors.affiliation: Department of Surgical and Morphological Sciences, School of Medicine, University of Insubria , Varese, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Lombardo
authors.affiliation: Department of Surgical and Morphological Sciences, School of Medicine, University of Insubria , Varese, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tedeschi
authors.affiliation: Department of Surgical and Morphological Sciences, School of Medicine, University of Insubria , Varese, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tosi
authors.affiliation: Department of Surgical and Morphological Sciences, School of Medicine, University of Insubria , Varese, Italy.
authors.forename: Roberto S
authors.initials: RS
authors.lastname: Accolla
keywords: CD4+ T cells; CIITA; DC; MHC class II