An epithelial cell line that can stimulate alloproliferation of resting CD4(+) T cells, but not after IFN-gamma stimulation

It has previously been shown that IFN-gamma-induced up-regulation of HLA cl ass II on the surface of epithelial cells is not sufficient to induce proli feration of allospecific CD4(+) T cells in vitro. To further investigate th is phenomenon, a human epithelial bladder carcinoma, T24, was induced to co nstitutively express HLA class II without IFN-gamma stimulation, by permane nt transfection with the full-length class II transactivator (CIITA) gene. Proliferation of allospecific T cells to transfected and wild-type cells wi th and without prior activation with saturating levels of IFN-gamma for 4 d ays was examined. IFN-gamma-activated T24 did not induce any response from CD4(+) T cells. However, T24.CIITA induced significant levels of alloprolif eration, which could be abrogated by pretreatment of T24,CIITA with a mAb t o LFA-3. Prestimulation of T24.CIITA with saturating levels of IFN-gamma fo r 4 days also prevented allospecific CD4(+) T cell proliferation. These fin dings suggest that epithelial cells may be intrinsically able to process an d present alloantigen and provide adequate costimulation, We propose that I FN-gamma has a secondary, as yet unidentified, effect that acts to negative ly regulate this response, at least in some epithelial cells.