B7-2 regulates survival, phenotype, and function of APCs.
The absence of B7-2-mediated costimulation protects NOD mice from the development of diabetes. Although the effects of B7-2 on T cell priming are well known, its impact on the function of APCs is not fully elucidated. We tested APC function and survival in mice lacking B7-2. A significant reduction in the phagocytic ability was observed in both splenic and pancreatic lymph node-associated dendritic cells (DCs) in B7-2 knockout (KO) mice. DCs from B7-2KO mice exhibited enhanced susceptibility to death, which was reflected by their reduced total cell numbers. Phenotypic analysis of APCs in B7-2KO mice revealed a significantly decreased proportion of CD8alpha+CD205+ DCs. Interestingly, an enhanced proportion of B7-H1+ and B7-DC+ DCs were observed in B7-2KO mice. Lastly, we found that B7-2 deficiency significantly diminished the PKC-epsilon response in APCs upon CD28-Ig stimulation. In conclusion our data suggests that B7-2 promotes the generation of a mature APC repertoire and promotes APC function and survival.
Yadav
Deepak
D
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Sarvetnick
Nora
N
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051940:B7-2 Antigen / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002462:Cell Membrane / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D016130:Immunophenotyping; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D010587:Phagocytosis / Q000235:genetics; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D051940:B7-2 Antigen; D051744:Protein Kinase C-epsilon