Reconstitution of allogeneic hemopoietic stem cells: the essential role of FcR gamma and the TCR beta-chain-FCp33 complex
Taylor, K.N.; Shinde Patil, V.R.; Colson, Y.L.
Journal of Immunology 177(3): 1444-1450
2006
ISSN/ISBN: 0022-1767 PMID: 16849450 Document Number: 597664
Transplantation of purified allogeneic hemopoietic stem cells (SC) alone is characterized by a decreased risk of graft-vs-host disease but increased incidence of engraftment failure. It has been established that the facilitating cell (FC) promotes allogeneic SC reconstitution and results in donor-specific transplantation tolerance across MHC disparities, without graft-vs-host disease. Although the requirements for this facilitating function are not well-characterized, it is known that facilitation is dependent on FC expression of a unique heterodimer consisting of the TCR beta-chain (TCR beta) and a 33-kDa protein, FCp33. The current study confirms that CD3 epsilon and TCR beta expression are present on the FC at the time of transplantation and demonstrates that the majority of cells in the FC population express the TCR signaling molecule, FcR gamma, rather than the more conventional CD3 zeta receptor. Of particular significance, we have now demonstrated that FC-mediated allogeneic SC reconstitution is critically dependent on FcR gamma expression and that FcR gamma coprecipitates with the TCR beta-FCp33 heterodimer. The mandatory requirement of TCR beta and FcR gamma for FC function provides the first evidence of a previously undescribed role for FcR gamma in the facilitation of allogeneic SC reconstitution and establishes that FcR gamma is part of the TCR beta-FCp33 complex uniquely expressed on FC.