Soluble MHC class I molecules induce cellular death in a CD8+T-cell hybridoma tumor model

Abstract

T cells undergo activation-induced cell death (AICD) after T-cell receptor cross-linking in the absence of co-stimulation. In this study, we examined whether AICD induced by purified MHC class I molecules could be used to selectively eliminate tumor cells in T-cell malignancies. As a model, soluble H-2Kb molecules refolded with the chicken ovalbumin SIINFEKL peptide (Kb-OVA) and a CD8+ T-cell hybridoma (CD8-OVA) specific for this peptide were used. Addition of CD8-OVA hybridoma cells to plastic plates adsorbed with Kb-OVA molecules resulted in a concentration-dependent decrease in cellular proliferation. Exogenous IL-4 further depressed the proliferation of CD8-OVA cells in a dose-dependent manner in the presence, but not in the absence, of Kb-OVA. Staining of these cells with propidium iodide confirmed that the decrease in cellular proliferation was due to apoptosis. The cytotoxic effect of plastic-immobilized Kb-OVA could be mimicked by soluble Kb-OVA tetramers. Furthermore, co-injection of Kb-OVA tetramers and CD8-OVA cells into mice suppressed the tumorigenicity of CD8-OVA cells. In conclusion, we describe a system whereby soluble MHC class I molecules can be used to selectively induce cellular death in a monoclonal T-cell tumor model. With future development, the use of MHC molecules may help to eliminate specific T cells in cases of T-cell malignancy and auto-immunity. © 2001 Wiley-Liss, Inc.