| First Author | Ueno T | Year | 2012 |
| Journal | Eur J Immunol | Volume | 42 |
| Issue | 9 | Pages | 2343-53 |
| PubMed ID | 22733595 | Mgi Jnum | J:187942 |
| Mgi Id | MGI:5438760 | Doi | 10.1002/eji.201242501 |
| Citation | Ueno T, et al. (2012) Intact B7-H3 signaling promotes allograft prolongation through preferential suppression of Th1 effector responses. Eur J Immunol 42(9):2343-53 |
| abstractText | Ligands of the B7 family provide both positive and negative costimulatory signals to the CD28 family of receptors on T lymphocytes, the balance of which determines the immune response. B7-H3 is a member of the B7 family whose function in T-cell activation has been the subject of some controversy: in autoimmunity and tumor immunity, it has been described as both costimulatory and coinhibitory, while in transplantation, B7-H3 signaling is thought to contribute to graft rejection. However, we now demonstrate results to the contrary. Signaling through a putative B7-H3 receptor prolonged allograft survival in a fully MHC-mismatched cardiac model and promoted a shift toward a Th2 milieu; conversely, B7-H3 blockade, achieved by use of a blocking antibody, resulted in accelerated rejection, an effect associated with enhanced IFN-gamma production. Finally, graft prolongation achieved by CTLA4 Ig was shortened both by B7-H3 blockade and the absence of recipient B7-H3. These findings suggest a coinhibitory role for B7-H3. However, experience with other CD28/B7 family members suggests that immune redundancy plays a crucial role in determining the functions of various pathways. Given the abundance of conflicting data, it is plausible that, under differing conditions, B7-H3 may have both positive and negative costimulatory functions. |
