γδ T Cells Do Not Require Fully Functional Cytotoxic Pathways or the Ability to Recognize Recipient Alloantigens to Prevent Graft Rejection

γδ T cells are a unique and minor T-cell subset that differs from conventional αβ T cells by virtue of their tissue localization and antigen processing requirements. We have previously shown that ex vivo–activated γδ T cells are able to prevent graft rejection without causing clinically significant graft-versus-host disease (GVHD). In the present study, we examined how γδ T cells facilitate alloengraftment and to what extent mechanisms used by conventional αβ T cells are also used by γδ T cells. We observed that, unlike αβ T cells, for which CD8+ T cells are primarily responsible for facilitating engraftment, purified CD8+γδ+ T cells administered at the same fractional dose as for the unseparated activated γδ T-cell population were insufficient to prevent graft rejection. Furthermore, the ability to prevent graft rejection was not affected by the absence of fully functional fas ligand or perforin cytotoxic pathways, nor was it contingent on the ability of γδ T cells to recognize recipient major histocompatibility process alloantigens. Repetitive infusions of a suboptimal dose of γδ T cells however were able to rescue mice from graft rejection, suggesting that the persistence of these cells in vivo was critical in facilitating alloengraftment. These studies demonstrate that γδ T cells do not use mechanisms used by conventional nontolerant αβ T cells to prevent graft rejection. The ability of these cells to promote engraftment without causing GVHD further distinguishes these cells from αβ T cells and may be an attribute that can be exploited in the clinical transplantation setting.