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Yoshihiko Usui, Youko Okunuki, Takaaki Hattori, Masaru Takeuchi, Takeshi Kezuka, Hiroshi Goto, Masahiko Usui; Expression of Costimulatory Molecules on Human Retinoblastoma Cells Y-79: Functional Expression of CD40 and B7H1. Invest. Ophthalmol. Vis. Sci. 2006;47(10):4607-4613. doi: 10.1167/iovs.06-0181.
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purpose. To examine the expression of various costimulatory molecules on the human retinoblastoma cell line Y-79 and assess the functional roles of selected costimulatory molecules.
methods. Y-79 cells were incubated in the presence or absence of IFN-γ, with or without irradiation (100 Gy). Expression of major histocompatibility complex (MHC) class I molecules, MHC class II, CD80, CD86, CD40, CD70, B7H1, B7DC, B7H2, OX40L, and 4-1BBL on Y-79 cells was measured by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometric analysis. The functional role of CD40-mediated interactions in modifying immune responses to Y-79 was assessed in vitro by using recombinant human CD40 ligand (rhCD40L). The costimulatory effect of B7H1-expressing IFN-γ–treated Y-79 cells on proliferation of purified T cells was studied in Y-79/T-cell coculture experiments with a blocking anti-B7H1 monoclonal antibody (mAb).
results. CD40 and B7H2 were consistently detected on Y-79 cells by RT-PCR and flow cytometry. Cell surface expression of CD40 was upregulated on stimulation by IFN-γ alone, radiation alone, and IFN-γ combined with radiation. B7H1 expression was induced by IFN-γ stimulation and increased further when irradiated Y-79 cells were stimulated by IFN-γ. Treatment of Y-79 cells with rhCD40L enhanced cell surface expression of MHC class I and intercellular adhesion molecule (ICAM)-1 and also stimulated monocyte chemotactic protein (MCP)-1 production. Proliferative response of purified CD3+ T cells costimulated with IFN-γ–stimulated Y-79 was significantly enhanced by the addition of anti-B7H1 mAb.
conclusions. These results suggest that CD40 expressed on Y-79 plays an important role in augmenting antitumor immunity. In contrast, the expression of B7H1 on IFN-γ–treated Y-79 cells contributes to the suppression of T cells. The dual effects of CD40 and B7H1 on Y-79 cells may contribute to positive or negative regulation of antitumor immune responses in human retinoblastoma.
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