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Expression of Costimulatory Molecules on Human Retinoblastoma Cells Y-79: Functional Expression of CD40 and B7H1

From the Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan.

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-, 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-–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- alone, radiation alone, and IFN- combined with radiation. B7H1 expression was induced by IFN- stimulation and increased further when irradiated Y-79 cells were stimulated by IFN-. 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-–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-–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.