CD40 cross-linking enhances the immunogenicity of Burkitt's-lymphoma cell lines

Epstein-Barr-virus (EBV)-positive Burkitt's-lymphoma (BL) cell lines are no t recognized by EBV-specific T cells, due to their non-immunogenic phenotyp e and restricted expression of latent EBV genes. We tested whether triggeri ng of CD40 can alter the phenotype of the tumor cells with regard to: (i) e xpression of surface markers, (ii) expression of viral antigens, (iii) pres entation of endogenous antigens to MHC-class-I restricted cytotoxic T lymph ocytes (CTLs), (iv) stimulatory capacity in allogeneic mixed-lymphocyte cul tures (MLCs), (v) sensitivity to natural-killer (NK)-cell-mediated lysis, C o-culture of EBV-positive BL cells with CD40-ligand-transfected L cells ind uced up-regulation of CD54 and CD80 but did not affect the expression of vi ral genes. In spite of significant up-regulation of TAP1 and TAP2, and incr eased expression of MHC class I, the BL cells remained unable to present en dogenously expressed viral antigens to EBV-specific CTL. However, the up-re gulation of adhesion and co-stimulatory molecules was associated with incre ased stimulatory capacity in MLC and enhanced sensitivity to NK cells. Thes e findings indicate that, while inducing only a modest phenotype shift, cro ss-linking of CD40 under physiologic conditions may selectively enhance the sensitivity of BL cells to anti-tumor immune responses. (C) 1999 Wiley-Lis s, Inc.