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Publication : Regulation of immunostimulatory function and costimulatory molecule (B7-1 and B7-2) expression on murine dendritic cells.

First Author  Larsen CP Year  1994
Journal  J Immunol Volume  152
Issue  11 Pages  5208-19
PubMed ID  7514631 Mgi Jnum  J:18346
Mgi Id  MGI:66344 Doi  10.4049/jimmunol.152.11.5208
Citation  Larsen CP, et al. (1994) Regulation of immunostimulatory function and costimulatory molecule (B7-1 and B7-2) expression on murine dendritic cells. J Immunol 152(11):5208-19
abstractText  Dendritic cells (DC) play a critical role in the initiation of T cell-mediated immune responses, and express costimulatory molecules that are required for optimal activation of unprimed T cells. Studies on the regulation of the costimulatory molecules on DC have produced evidence from several systems that GM-CSF can up-regulate expression of CTLA4 counter receptor (CTLA4-CR) (but not intercellular adhesion molecule 1 (ICAM-1) and heat stable Ag (HsAg)) on DC. This is demonstrated on splenic DC, Langerhans cells, kidney DC in culture, and in a skin-explant culture system, in which the increased expression of CTLA4-CR on Langerhans cells (LC) occurs concomitantly with their migration out of skin. Interestingly, despite the ability of both GM-CSF and IFN-gamma to increase CTLA4-CR and maintain similar levels of ICAM-1, HsAg, and MHC molecule expression, the functional consequences of these cytokines on splenic DC are distinctly different. GM-CSF enhances the ability of DC to stimulate both T cell proliferation and cytokine release, whereas IFN-gamma causes no increase in immunostimulatory function. Further analysis of the CTLA4-CR on these cell populations by using the GL-1 and IG10 mAbs has shown that GM-CSF-cultured DC express high levels of both B7-1 and B7-2, whereas IFN-gamma-cultured DC express increased levels of only B7-2. These results suggest that optimal stimulation of unprimed T cells to proliferate and release cytokines may require participation of both of these CTLA4 counter receptors, and confirm the importance of GM-CSF for the maturation of DC into potent stimulators of T cell activation.
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