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

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 sel ectively eliminate tumor cells in T-cell malignancies. As a model. soluble H-2K(b) molecules refolded with the chicken ovalbumin SIINFEKL peptide (K-b -OVA) and a CD8(+) T-cell hybridoma (CD8-OVA) specific for this peptide wer e used. Addition of CD8-OVA hybridoma cells to plastic plates adsorbed with K-b-OVA molecules resulted in a concentration-dependent decrease in cellul ar proliferation. Exogenous IL-4 further depressed the proliferation of CD8 -OVA cells in a dose-dependent manner in the presence, but not in the absen ce, of K-b-OVA. Staining of these cells with propidium iodide confirmed tha t the decrease in cellular proliferation was due to apoptosis. The cytotoxi c effect of plastic-immobilized K-b-OVA could be mimicked by soluble K-b-OV A tetramers. Furthermore, coinjection of K-b-OVA tetramers and CD8-OVA cell s 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 s electively induce cellular death in a monoclonal T-cell tumor model. With f uture development, the use of MHC molecules may help to eliminate specific T cells in cases of T-cell malignancy and auto-immunity. (C) 2001 Wiley-Lis s, Inc.