Sustained Treg expansion by repeated in vivo injection of anti-TNFRSF25 mAb (P4142)

• Published in: The Journal of immunology (1950) 2013-05, Vol.190 (1_Supplement), p.191-191.17
• Main Authors: Zhang, Hong, Pahuja, Anil, Lundsten, Kelly, Li, Sky, Lin, Xiao, Ransom, John, Yang, Xi Feng
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.190.Supp.191.17

FOXP3+ Tregs play key roles in maintenance of immune tolerance and autoimmune reactions. TNFRSF25 (also known as DR3) is one of the more recently discovered TNFRSF member, which is expressed by mouse Tregs, naïve CD4, CD8, NKT cells and TLR4-induced DC and macrophages. A significant Treg in vivo expansion by TNFRSF25 stimulation has been reported. Here, we show that by single dose i.p. injection of an agonistic mAb, 4C12, Treg expansion starts to be observed on day 3, reached a peak (up to 30-40% of total CD4+ T-cells) on day 5-6, and then returned to baseline (5-7%) by day 10. Upon repeated 3-day interval injections, high level (about 20%) of expanded Tregs can be sustained more than 10 days. As reported by other authors, followed by one dose 4C12 injection, the absolute number of CD8+T cells, B cells, dendritic cells and macrophages was not affected. In the in vitro study, 4C12 antibody did not significantly induce Treg expansion in CD3/CD28/IL-2 culture system. Moreover, we characterized the TNFRSF25 expanded Tregs in vivo, we found that the expression level of CD304, CD152, Helio, GARP, LAP (TGF-b1), FR4, GITR was significantly increased in comparison to the control. These data suggest that multiple injections of 4C12 can long term sustain expanded Tregs at certain level, the biological significance of Treg need to be further studied.