PT  - JOURNAL ARTICLE
AU  - Böhm, Waltraud
AU  - Thoma, Stefan
AU  - Leithäuser, Frank
AU  - Möller, Peter
AU  - Schirmbeck, Reinhold
AU  - Reimann, Jörg
TI  - T Cell-Mediated, IFN-γ-Facilitated Rejection of Murine B16 Melanomas
DP  - 1998 Jul 15
TA  - The Journal of Immunology
PG  - 897--908
VI  - 161
IP  - 2
4099  - http://www.jimmunol.org/content/161/2/897.short
4100  - http://www.jimmunol.org/content/161/2/897.full
SO  - J. Immunol.1998 Jul 15; 161
AB  - The murine melanoma cell line B16.F10 (H-2b) was used to study specific T cell responses that reject tumors. Stable B16 transfectants were established that express viral Ags, either the hepatitis B surface Ag (HBsAg) or the large tumor Ag (T-Ag) of SV40. B16 cells and their transfected sublines were CD40+CD44+ but expressed no (or low levels of the) costimulator molecules CD154 (CD40L), CD48, CD54, CD80, and CD86. Surface expression of MHC class I (Kb, Db) and class II (I-Ab) molecules by B16 cells was low, but strikingly up-regulated by IFN-γ. CD95 (Fas) and CD95 ligand (CD95L (FasL)) were “spontaneously” expressed by B16 cells growing in vitro in serum-free medium; these markers were strikingly up-regulated by IFN-γ. B16 cells coexpressing CD95 and CD95L were irreversibly programed for apoptosis. In vitro, noninduced B16 transfectants stimulated a specific IFN-γ release response, but no cytolytic response (in a 4-h assay) in MHC class I-restricted CTL; in contrast, IFN-γ-induced B16 targets were efficiently and specifically lysed by CTL. In vivo, B16 transfectants were specifically rejected by DNA-vaccinated syngeneic hosts through a T-dependent immune effector mechanism. The tumors showed evidence of massive apoptosis in vivo during the rejection process. The data suggest that CTL-derived IFN-γ enhances an intrinsic suicide mechanism of these tumor cells in addition to facilitating lytic interactions of effectors with tumor targets.