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
✍ Scribed by Kai Kronfeld; Hinrich Abken; Barbara Seliger
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- French
- Weight
- 148 KB
- Volume
- 117
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
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‐γ 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‐γ 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‐α 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. © 2005 Wiley‐Liss, Inc.