An inflammatory checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral tissues

作者：Chakraverty Ronjon; Cote Daniel; Buchli Jennifer; Cotter Pete; Hsu Richard; Zhao Guiling; Sachs Teviah; Pitsillides Costas M; Bronson Roderick; Means Terry; Lin Charles; Sykes Megan^*

来源：Journal of Experimental Medicine, 2006, 203(8): 2021-2031.

DOI：10.1084/jem.20060376

Transfer of T cells to freshly irradiated allogeneic recipients leads to their rapid recruitment to nonlymphoid tissues, where they induce graft-versus-host disease (GVHD). In contrast, when donor T cells are transferred to established mixed chimeras (MCs), GVHD is not induced despite a robust graft-versus-host (GVH) reaction that eliminates normal and malignant host hematopoietic cells. We demonstrate here that donor GVH-reactive T cells transferred to MCs or freshly irradiated mice undergo similar expansion and activation, with similar up-regulation of homing molecules required for entry to nonlymphoid tissues. Using dynamic two-photon in vivo microscopy, we show that these activated T cells do not enter GVHD target tissues in established MCs, contrary to the dogma that activated T cells inevitably traffic to nonlymphoid tissues. Instead, we show that the presence of inflammation within a nonlymphoid tissue is a prerequisite for the trafficking of activated T cells to that site. Our studies help to explain the paradox whereby GVH-reactive T cells can mediate graft-versus-leukemia responses without inducing GVHD in established MCs.

• 出版日期2006-8-7