Attenuation of the Fas-L independent B16BL6 melanoma lymphocidic capacity by H-2K class I molecules.
We have previously reported that the capacity of highly malignant B16BL6 murine melanoma cells to induce cell death in naive syngeneic lymphocytes stems from the absence of major histocompatibility complex (MHC) class I glycoproteins in these melanoma cells. Our present study provides evidence that the above-mentioned lymphocidic activities of B16BL6 cells are selectively attenuated when the expression of H-2K (but not H-2D or H-2L) MHC class I glycoproteins is reconstituted in these cells. The induction of apoptosis in naive lymphocytes by H-2K-deficient melanoma cells does not involve the Fas ligand (Fas-L)/FAS signaling module, as demonstrated by employing lymphocytes derived from Fas-L(gld)- or Fas(lpr)-deficient mice in co-culture experiments. Furthermore, these tumor cells fail to induce Fas-L-mediated fratricide in co-cultured lymphocytes and do not express Fas-L either when grown alone or co-cultured with lymphocytes. These findings explain the previously widely reported selective down-regulation of certain MHC class I-encoded glycoproteins (H-2K, bur not H-2D or H-2L) during tumor progression. Namely, the initiation of an effective immune response against H-2K-deficient cells could be abrogated at very early steps, as the result of the induction of Fas-L/Fas-independent cell death among naive lymphoid cells.
Kellman-Pressman
Sigal
S
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL, USA.
Fishman
Daniel
D
Tsory
Sylvia
S
Segal
Shraga
S
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D018920:Coculture Techniques; D053222:Fas Ligand Protein; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D008214:Lymphocytes / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000276:immunology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D064532:Histocompatibility Antigen H-2D; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D048069:Tumor Necrosis Factors