A repertoire-independent and cell-intrinsic defect in murine GVHD induction by effector memory T cells
- 1 December 2011
- journal article
- Published by American Society of Hematology in Blood
- Vol. 118 (23), 6209-6219
- https://doi.org/10.1182/blood-2011-01-330035
Abstract
Effector memory T cells (TEM) do not cause graft-versus-host disease (GVHD), though why this is has not been elucidated. To compare the fates of alloreactive naive (TN) or memory (TM) T cells, we developed a model of GVHD in which donor T cells express a transgene-encoded TCR specific for an antigenic peptide that is ubiquitously expressed in the recipient. Small numbers of naive TCR transgenic (Tg) T cells induced a robust syndrome of GVHD in transplanted recipients. We then used an established method to convert TCR Tg cells to TM and tested these for GVHD induction. This allowed us to control for the potentially different frequencies of alloreactive T cells among TN and TM, and to track fates of alloreactive T cells after transplantation. TEM caused minimal, transient GVHD whereas central memory T cells (TCM) caused potent GVHD. Surprisingly, TEM were not inert: they, engrafted, homed to target tissues, and proliferated extensively, but they produced less IFN-γ and their expansion in target tissues was limited at later time points, and local proliferation was reduced. Thus, cell-intrinsic properties independent of repertoire explain the impairment of TEM, which can initiate but cannot sustain expansion and tissue damage.Keywords
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