B7-1 and B7-2 act differentially in the induction of a T cell response: their impact for a HLA-matched and HLA-mismatched anti-tumor immunotherapy.
The efficacy of T cell-based immunotherapy is primarily due to efficient cellular activation that requires the engagement of 2 separate signals, i.e., via the T cell receptor complex and via co-stimulatory molecules the prototype of which is CD28. In cellular activation, the CD28 ligands B7-1 (CD80) and B7-2 (CD86) are thought to play nearly identical roles in T cell activation. We monitored the T cell response upon co-culture with HLA Class I-matched and mismatched renal carcinoma cells, respectively, that express different levels of B7-1 and B7-2, respectively. In a HLA Class I-mismatched co-culture, T cell proliferation, IFN-gamma and GM-CSF secretion equally depend on the levels of B7-1 and B7-2 on tumor cells. In contrast, in a HLA Class I-matched situation, B7-2 is more effective in the induction of IFN-gamma and GM-CSF secretion than B7-1, but both B7 molecules induce T cell proliferation equally efficient. B7-2 is more effective than B7-1 in inducing TNF-alpha and IL-10 secretion in both HLA Class I-matched and mismatched situations. The distinct patterns of cytokine induction by B7-1 and B7-2 obviously depend on the HLA Class I compatibility. These conclusions have substantial implications for the development of B7-based vaccines used for immunotherapies.
Coordination Center for Clinical Trials (KKS) Mainz, Johannes Gutenberg University, Mainz, Germany.
Kai
K
Kronfeld
Hinrich
H
Abken
Barbara
B
Seliger
D018122:B7-1 Antigen / Q000276:immunology*; D051940:B7-2 Antigen / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000628:therapy; D045744:Cell Line, Tumor; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000276:immunology* / Q000628:therapy; D007959:Lymphocyte Culture Test, Mixed; D013601:T-Lymphocytes / Q000276:immunology*
D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D006680:HLA Antigens