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J Exp Med. 2006 Aug 7;203(8):2021-31. Epub 2006 Jul 31.

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

Author information

1
Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.

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.

PMID:
16880259
PMCID:
PMC2118376
DOI:
10.1084/jem.20060376
[Indexed for MEDLINE]
Free PMC Article

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