D. Mumberg et al., CD4(+) T cells eliminate MHC class II-negative cancer cells in vivo by indirect effects of IFN-gamma, P NAS US, 96(15), 1999, pp. 8633-8638
Citations number
42
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
CD4(+) T cells can eliminate tumor cells in vivo in the absence of CD8(+) T
cells. We have CD4(+) T cells specific for a MHC class II-restricted, tumo
r-specific peptide derived from a mutant ribosomal protein expressed by the
UV light-induced tumor 6132A-PRO. By using neutralizing mAb specific for m
urine IFN-gamma and adoptive transfer of CD4(+) T cells into severe combine
d immunodeficient mice, we show that anti-IFN-gamma treatment abolishes the
CD4(+) T cell-mediated rejection of the tumor cells in vivo. The tumor cel
ls were MHC class II negative, and IFN-gamma did not induce MHC class II ex
pression in vitro. Therefore, the tumor-specific antigenic peptide must be
presented by host cells and not the tumor cells. Tumor cells transduced to
secrete IFN-gamma had a markedly reduced growth rate in severe combined imm
unodeficient mice, but IFN-gamma did not inhibit the growth of the tumor ce
lls in vitro. Furthermore, tumor cells stably expressing a dominant-negativ
e truncated form of the murine IFN-gamma receptor a chain, and therefore in
sensitive to IFN-gamma, nevertheless were rejected by the adoptively transf
erred CD4(+) T cells. Thus, host cells, and not tumor cells, seem to be the
target of IFN-gamma. Together, these results show that CD4(+) T cells can
eliminate IFN-gamma-insensitive, MHC class II-negative cancer cells by an i
ndirect mechanism that depends on IFN-gamma.