CIUSSS Capitale nationale logo

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

Publication Type:

Journal Article

Source:

J Exp Med, Volume 203, Issue 8, p.2021-31 (2006)

Keywords:

Animals, CD8-Positive T-Lymphocytes, Cross-Priming, Graft vs Host Disease, Graft vs Host Reaction, Inflammation, Mice, Radiation Chimera, Skin, T-Lymphocytes, Toll-Like Receptors

Abstract:

<p>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.</p>

Funding / Support / Partners

logo FRQ-S logo ctrn logo fci logo cihr irsc logo nserc logo MESISentinelle nord