@article {542546,
	title = {An important role of CD80/CD86-CTLA-4 signaling during photocarcinogenesis in mice.},
	journal = {J Immunol},
	volume = {174},
	number = {9},
	year = {2005},
	month = {2005 May 1},
	pages = {5298-305},
	abstract = {Although previous studies have shown that altered B7 costimulation plays a critical role in UV irradiation-induced regulation of immunity, the individual roles of the B7 receptors (CD28 and CTLA-4) or the B7 family members (CD80 and CD86) have not been explored. Thus, we investigated CTLA-4 signaling during photocarcinogenesis of chronically UV-B-exposed mice using an antagonistic anti-CTLA-4 Ab. Anti-CTLA-4-treated mice developed significantly fewer UV-induced tumors. Moreover, anti-CTLA-4 treatment induced long-lasting protective immunity because progressively growing UV tumors inoculated into anti-CTLA-4- and UV-treated mice that had not developed tumors were rejected. Next, we used mice deficient for CD80, CD86, or both in photocarcinogenesis studies to assess the relative contributions of these CTLA-4 ligands. Double-deficient mice showed significantly reduced UV-induced skin tumor development, whereas CD86(-/-) mice produced skin cancer earlier compared with CD80(-/-) and control mice. The growth of UV-induced tumors appears to be controlled by UV-induced suppressor T cells, because CD80(-/-)/CD86(-/-) mice had strongly reduced numbers of UV-induced CD4(+)CD25(+) suppressor T cells. In vitro, CTLA-4 blockade inhibited the suppressor activity of UV-induced CD4(+)CD25(+) T cells, suggesting that reduced photocarcinogenesis might be due to decreased numbers or function of suppressor T cells. Together, these data indicate that blocking CD80/86-CTLA-4 signaling induced immune protection against the development of UV-induced skin tumors. Furthermore, CD86-mediated costimulation appears to play a more critical role in the protection against photocarcinogenesis than CD80.},
	keywords = {Animals, Antibodies, Blocking, Antigens, CD, Antigens, CD80, Antigens, CD86, Antigens, Differentiation, Bone Marrow Cells, Cell Line, Tumor, CTLA-4 Antigen, Dendritic Cells, Graft Rejection, Growth Inhibitors, Immunosuppressive Agents, Lymphocyte Activation, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, Mice, Knockout, Neoplasm Transplantation, Neoplasms, Radiation-Induced, Signal Transduction, Skin Neoplasms, T-Lymphocytes, Regulatory, Ultraviolet Rays},
	issn = {0022-1767},
	author = {Loser, Karin and Scherer, Andrea and Krummen, Mathias B W and Varga, Georg and Higuchi, Tetsuya and Schwarz, Thomas and Sharpe, Arlene H and Grabbe, Stephan and Bluestone, Jeffrey A and Beissert, Stefan}
}
