Chakraverty, R; Cote, D; Buchli, J; Cotter, P; Hsu, R; Zhao, GL; Sachs, T; ... Sykes, M; + view all Chakraverty, R; Cote, D; Buchli, J; Cotter, P; Hsu, R; Zhao, GL; Sachs, T; Pitsillides, CM; Bronson, R; Means, T; Lin, C; Sykes, M; - view fewer (2006) An inflammatory checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral tissues. J EXP MED , 203 (8) 2021 - 2031. 10.1084/jem.20060376.

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Abstract

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.

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