T-cell co-stimulation by the CD28 ligand B7 is involved in the immune response leading to rejection of a spontaneously regressive tumor
✍ Scribed by Pascal Chaux; Monique S. Martin; François Martin
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- French
- Weight
- 732 KB
- Volume
- 66
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Cell variants from experimental tumors may lose their tumorigenicity or give rise to tumors that regress after a short period of progression in immunocompetent syngeneic animals. Rejection of these tumor cells is often 1-cell-dependent. It has recently been reported that, besides the specific signal delivered through the clonogenic receptor, T-cell activation requires a co-stimulatory signal, delivered through its CD28 receptor by 87-1 and/or B7-2 molecules expressed at the surface of the antigen-presenting cells. CTLA4lg, a fusion molecule that specifically inhibits B7-I and B7-2 binding to their receptor on T cells, was used to investigate the role of B7 in the spontaneous regression of the tumors induced in syngeneic rats by REGb cells, a regressor cell line established from a chemically induced colon carcinoma. When rats received either I or 3 CTLA4lg injections, REGb tumors grew 3 or 7 times larger than in control animals, respectively. However, in most animals, single or repeated CTLA4lg injections delayed rather than suppressed REGb tumor rejection. Antibodies to CTLA4lg appeared in treated rats and could explain this transient effect. Neither REGb cells nor freshly isolated MHC class-ll+ antigen-presenting cells infiltrating REGb tumors expressed B7, establishing that the target of CTLA4lg was not located inside the tumor. In contrast, MHC class-ll+ B7+ accessory cells were found in the REGb tumor-draining lymph nodes, suggesting that lymphoid tissue, rather than the tumor itself, was the site of tumorantigen presentation to tumor-specific T cells. These results