Human LAP(+)GARP(+)FOXP3(+) regulatory T cells attenuate xenogeneic graft versus host disease

Wang, Huihui; Song, Hyo; Pham, Anha V.; Cooper, Laurence J.; Schulze, Janika J.; Olek, Sven; Tran, Dat Q.

Adoptive transfer of LAP + Tregs delayed the development of xenogeneic GVHD. Our finding supports a prior observation showing that GARP + Treg protect from xGVHD. Dr. Lucas group found that the administration of antibody blocking GARP or GARP/TGF-β1 abrogate the protection of Tregs in xGVHD [31] . While we are able to demonstrate the suppressive function of LAP + Tregs, these assays have limitations. Although the LAP + Tregs demonstrate suppressive function by delaying the development of xenogeneic GVHD, we are unable to detect their existence in peripheral blood and spleens of the NSG mice by day 14 post adoptive transfer. Similar to our finding, Parmar et al. have previously shown that ex vivo-expanded cord blood Tregs in NSG xenogeneic model did not persist beyond day 3 [26] . One possible explanation might be due to cytokine deprivation, particularly IL2. Enhancing the stability of LAP + Tregs is critical for the development of an efficacious cell therapy. At this point, we are unclear whether their lack of persistence is intrinsic to the human Tregs or extrinsic due to the absence of critical growth factors compatible with human Tregs in the NSG mice. Further studies are needed to answer these two issues.