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Title: An inflammatory checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral tissues
Authors: Chakraverty, Ronjon K. 
Côté, Daniel 
Pitsillides, Costas 
Keywords: T cells;Mice;Animal experimentation;Animal tissue;graft versus host reaction;Graft versus host disease;Inflammation
Issue Date: 2006
Publisher: Rockefeller University Press
Source: Journal of experimental medicine, 2006, Volume 203, Issue 8, Pages 2021-2031
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
ISSN: 0022-1007 (print)
1540-9538 (online)
DOI: 10.1084/jem.20060376
Rights: JEM © The Rockefeller University Press
Type: Article
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