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 selectively 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 were used. Addition of CD8-OVA hybridoma cells to plastic plates adsorbed with K(b)-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 K(b)-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 K(b)-OVA could be mimicked by soluble K(b)-OVA tetramers. Furthermore, co-injection of K(b)-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.
Kambayashi
T
T
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
Ichihara
F
F
Jensen
P E
PE
Ljunggren
H G
HG
D000818:Animals; D017209:Apoptosis; D016923:Cell Death / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004527:Egg Proteins / Q000627:therapeutic use*; D015395:Histocompatibility Antigens Class I / Q000627:therapeutic use*; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007202:Indicators and Reagents; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D010047:Ovalbumin / Q000627:therapeutic use*; D010446:Peptide Fragments; D011419:Propidium; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D004527:Egg Proteins; D015395:Histocompatibility Antigens Class I; D007202:Indicators and Reagents; C110366:OVA-8; D010446:Peptide Fragments; D015847:Interleukin-4; D011419:Propidium; D010047:Ovalbumin; D013936:Thymidine