CD80-transfected human breast and ovarian tumor cell lines: improved immunogenicity and induction of cytolytic CD8+ T lymphocytes.
Human tumor cell lines derived from breast and ovarian carcinomas have been found to be ineffective in stimulating the induction phase of an immune response such as T cell proliferation in allogeneic mixed tumor cell lymphocyte cultures. Since representative tumor cell lines are effectively lysed by activated T lymphocytes, the induction of an effector phase is not impaired. In order to reconstitute the potential to induce primary T cell activation, we transfected CD80 into a breast (KS) and an ovarian carcinoma (GG) cell line. CD80 expression in KS cells resulted in improved primary T cell activation, whereas it was ineffective in the case of GG cells. However, treatment of CD80-transfected GG cells with INF-gamma rendered them immunogenic, and resulted in T cell proliferation. Likewise, TNF-alpha and/or INF-gamma augmented T cell proliferation induced by CD80-transfected KS cells. Furthermore, T lymphocytes stimulated with cytokine-treated CD80+ KS cells gave rise to a long term proliferating CD8+ CTL line with class I MHC restricted cytolytic antitumor activity. These studies emphasize the requirement for costimulation in generating tumor-specific immunity, and demonstrate the efficacy of CD80 in generating CD8+ cytolytic T lymphocytes.
Gückel
B
B
Klinikum der Ruprecht-Karls-Universität, Frauenklinik, Heidelberg, Germany.
Lindauer
M
M
Rudy
W
W
Habicht
A
A
Siebels
M
M
Kaul
S
S
Bastert
G
G
Meuer
S C
SC
Moebius
U
U
D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000502:physiology*; D001943:Breast Neoplasms / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology; D008213:Lymphocyte Activation; D010051:Ovarian Neoplasms / Q000276:immunology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018122:B7-1 Antigen; D011994:Recombinant Proteins; D007371:Interferon-gamma