The Role of the Fc Region in CD70-specific Antibody Effects on Cardiac Transplant Survival

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

TitleThe Role of the Fc Region in CD70-specific Antibody Effects on Cardiac Transplant Survival
TypeJournal article
AuthorsJurcevic, 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.

JournalTransplantation
Journal citation92 (11), pp. 1194-1201
ISSN0041-1337
Year2011
PublisherWolters 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 ID22089665
Publication dates
Published15 Dec 2011

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