Mechanism of cytolytic T lymphocyte killing of a low class I-expressing tumor.
Many tumors have been shown to express minimal levels of class I MHC Ag, which makes them more resistant to recognition and lysis by cytolytic T lymphocytes. Line 1, a BALB/c spontaneous lung carcinoma, normally expresses very low levels of class I Ag, but expression can be increased 50-fold by treatment with agents such as DMSO or IFN-gamma. Because class I Ag serve as restricting elements for cytolytic T cell recognition of tumor Ag, we wished to determine if cytotoxic T lymphocytes could play a role in the immune response to this type of class I low, but inducible, tumor. After immunization in vivo and restimulation of splenic cells in vitro we were able to generate T cell clones that lysed line 1 cells induced to express high levels of class I, but did not lyse uninduced, low class I expressing line 1 cells in short term (6-h) 51Cr release assays. Paradoxically, incubation of the T cells with uninduced class I low line 1 cells for a few days resulted in complete destruction of the tumor cells. We demonstrate that the T cells, stimulated by the tumor cells, produce IFN-gamma, which in turn induces class I expression on the line 1 cells making them susceptible to lysis by the T cell clone. This suggests that a positive feedback reaction can occur in generating a response to this and perhaps other inducible tumor cell lines.
Blieden
T M
TM
Division of Immunology, University of Rochester Medical Center, NY 14642.
McAdam
A J
AJ
Frelinger
J G
JG
Lord
E M
EM
D000818:Animals; D002277:Carcinoma / Q000276:immunology*; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006183:H-2 Antigens / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D008175:Lung Neoplasms / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma; D004121:Dimethyl Sulfoxide