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

• Published in: Frontiers in immunology 2019-04, Vol.10, p.624-624
• Main Authors: Huang, Wei, Mo, Wenjian, Jiang, Jieling, Chao, Nelson J., Chen, Benny J.
• Format: Article
• Language: English
• Subjects: alloreactive memory T cells; GVHD; Immunology; OT-II; OVA; skin graft rejection; TCM
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.00624

Data from both animal models and humans have demonstrated that effector memory T cells (T EM ) and central memory T cells (T CM ) from unprimed donors have decreased ability to induce graft-vs-host disease (GVHD). Allospecific T EM from primed donors do not mediate GVHD. However, the potential of alloreactive T CM 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 high T CM 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 high T CM 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 + T CM respond to alloantigen during GVHD and underscore the fundamental difference of alloresponses mediated by allospecific T CM in graft rejection and GVHD settings.