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 class II on the surface of epithelial cells is not sufficient to induce proliferation of allospecific CD4+ T cells in vitro. To further investigate this phenomenon, a human epithelial bladder carcinoma, T24, was induced to constitutively express HLA class II without IFN-gamma stimulation, by permanent transfection with the full-length class II transactivator (CIITA) gene. Proliferation of allospecific T cells to transfected and wild-type cells with and without prior activation with saturating levels of IFN-gamma for 4 days was examined. IFN-gamma-activated T24 did not induce any response from CD4+ T cells. However, T24.CIITA induced significant levels of alloproliferation, which could be abrogated by pretreatment of T24.CIITA with a mAb to LFA-3. Prestimulation of T24. CIITA with saturating levels of IFN-gamma for 4 days also prevented allospecific CD4+ T cell proliferation. These findings suggest that epithelial cells may be intrinsically able to process and present alloantigen and provide adequate costimulation. We propose that IFN-gamma has a secondary, as yet unidentified, effect that acts to negatively regulate this response, at least in some epithelial cells.
Lawson
C
C
Transplant Immunology Group, Imperial College School of Medicine, National Heart and Lung Institute, Heart Science Centre, Harefield Hospital, Harefield, Middlesex, United Kingdom.
McCormack
A M
AM
Moyes
D
D
Yun
S
S
Fabre
J W
JW
Yacoub
M
M
Rose
M L
ML
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018968:CD58 Antigens / Q000276:immunology; D002460:Cell Line; D017635:Clonal Anergy / Q000235:genetics / Q000276:immunology; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D006681:HLA-D Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007399:Interphase / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D009687:Nuclear Proteins; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D014162:Transfection / Q000276:immunology
D018968:CD58 Antigens; D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D007106:Immune Sera; D007376:Interleukin-2; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D007371:Interferon-gamma