Jurcevic, S., Shariff, H., Greenlaw, R.E., Meader, L., Gardner, N., Yagita, H., Coccia, M. and Mamode, N. 2011. The Role of the Fc Region in CD70-specific Antibody Effects on Cardiac Transplant Survival. Transplantation. 92 (11), pp. 1194-1201. https://doi.org/10.1097/TP.0b013e3182347ecd
| Title | The Role of the Fc Region in CD70-specific Antibody Effects on Cardiac Transplant Survival |
|---|---|
| Type | Journal article |
| Authors | Jurcevic, S., Shariff, H., Greenlaw, R.E., Meader, L., Gardner, N., Yagita, H., Coccia, M. and Mamode, N. |
| Abstract | Background: The role of the CD70-specific antibody and the mechanisms by which it extends transplant survival are not known. Methods: Fully major histocompatibility complex-mismatched heterotopic heart transplantation (BALB/c to C57BL/6) was performed. Treated mice received intraperitoneal injections of wild-type (WT) CD70-specific antibody (FR70) or IgG1 or IgG2a chimeric antibodies on days 0, 2, 4, and 6 posttransplantation. Results: WT FR70 antibody significantly extended heart transplant survival to 19 days compared with untreated mice (median survival time [MST]=10 days). Graft survival using the nondepleting IgG1 antibody was significantly shorter (MST=14 days), whereas the survival using depleting IgG2a antibody (MST=18) was similar to that using WT FR70. The FR70 and IgG2a antibodies demonstrated a greater efficiency of fixing mouse complement over the IgG1 variant in vitro. CD4 and CD8 T-cell graft infiltration was reduced with treatment; however, this was most pronounced with WT FR70 and IgG2a antibody therapy compared with the IgG1 chimeric variant. Circulating donor-specific IgG alloantibodies were initially reduced with WT FR70 treatment (day 8 posttransplantation) but increased at days 15 and 20 posttransplantation to the level detected in untreated controls. Conclusion: We conclude that WT (FR70) and the IgG2a depleting variant of CD70-specific antibody reduce graft infiltrating CD4 and CD8 T cells, transiently reduce serum alloantibody levels, and extend graft survival. In contrast, the nondepleting IgG1 variant of this antibody showed lower efficacy. These data suggest that a depleting mechanism of action and not merely costimulation blockade plays a substantial role in the therapeutic effects of CD70-specific antibody. |
| Journal | Transplantation |
| Journal citation | 92 (11), pp. 1194-1201 |
| ISSN | 0041-1337 |
| Year | 2011 |
| Publisher | Wolters Kluwer |
| Accepted author manuscript | File Access Level Open (open metadata and files) |
| Publisher's version | File Access Level Open (open metadata and files) |
| Digital Object Identifier (DOI) | https://doi.org/10.1097/TP.0b013e3182347ecd |
| PubMed ID | 22089665 |
| Publication dates | |
| Published | 15 Dec 2011 |