AUTHOR=Huang Wei , Mo Wenjian , Jiang Jieling , Chao Nelson J. , Chen Benny J. 

TITLE=Donor Allospecific CD44high Central Memory T Cells Have Decreased Ability to Mediate Graft-vs.-Host Disease

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00624

DOI=10.3389/fimmu.2019.00624

ISSN=1664-3224

ABSTRACT=<p>Data from both animal models and humans have demonstrated that effector memory T cells (T<sub>EM</sub>) and central memory T cells (T<sub>CM</sub>) from unprimed donors have decreased ability to induce graft-vs-host disease (GVHD). Allospecific T<sub>EM</sub> from primed donors do not mediate GVHD. However, the potential of alloreactive T<sub>CM</sub> to induce GVHD is not clear. In this study, we sought to answer this question using a novel GVHD model induced by T cell receptor (TCR) transgenic OT-II T cells. Separated from OT-II mice immunized with OVA protein 8 weeks earlier, the allospecific CD44<sup>high</sup> T<sub>CM</sub> were able to mediate skin graft rejection after transfer to naive mice, yet had dramatically decreased ability to induce GVHD. We also found that these allospecific CD44<sup>high</sup> T<sub>CM</sub> persisted in GVHD target organs for more than 30 days post-transplantation, while the expansion of these cells was dramatically decreased during GVHD, suggesting an anergic or exhausted state. These observations provide insights into how allospecific CD4<sup>+</sup> T<sub>CM</sub> respond to alloantigen during GVHD and underscore the fundamental difference of alloresponses mediated by allospecific T<sub>CM</sub> in graft rejection and GVHD settings.</p>