Abstract We showed that overexpression of CD200, a molecule of the immunoglobulin supergene family, increases graft survival and suppresses inflammation/acquired immunity after binding to its receptors (CD200Rs). Skin/cardiac allograft survival is increased in transgenic mice over-expressing CD200 under control of a doxycycline-inducible promoter, (CD200tg), or following transplantation of CD200tg grafts to control mice, along with increased intra-graft expression of mRNAs implicated in Treg differentiation, including TGFβ, IL-10 and Foxp3. We have investigated whether C57BL/6 CD200tg grafts taken from control BALB/c mice at 14 days post transplantation can be successfully re-grafted into secondary control BALB/c mice, and whether such animals show perturbation of specific alloimmunity, and/or changes in graft gene expression in comparison to mice receiving control C57BL/6 grafts. Control grafts taken from mice at d14 and re-transplanted to control BALB/c mice were rejected rapidly, and with mice developing the expected CTL response in splenocytes detected by lysis of EL4 tumor targets in 4-hour 51Cr-release assays. In contrast, CD200tg grafts survived on secondary transfer to control BALB/c mice, with specific suppression of the cytotoxicitv response to EL4 targets. In these secondary recipients only, persistently high expression of Foxp3, IL-10 and TGFβ gene expression was seen. We conclude that expression of these latter genes is crucial for adoptive transfer of tolerance.