Allospecific CD4(+) Effector Memory T Cells Do Not Induce Graft-versus-Host Disease in Mice

作者：Zhang, Ping; Wu, Jieying; Deoliveira, Divino; Chao, Nelson J.; Chen, Benny J.^*

来源：Biology of Blood and Marrow Transplantation, 2012, 18(10): 1488-1499.

DOI：10.1016/j.bbmt.2012.07.009

• Clonal deletion
• Clonal anergy
• Organ transplantation
• T cell exhaustion
• T cell tolerance
• T cell memory

We studied whether allospecific CD4(+) effector memory T cells (T-EM) could induce graft-versus-host disease (GVHD) using a novel GVHD model induced solely by CD4(+) T cell receptor transgenic TEa cells. Allospecific T-EM generated in a lymphopenic host bore a typical memory phenotype. Moreover, these cells were able to elicit a faster and more effective proliferative response on challenge with alloantigen in vitro and to mediate "second-set" skin graft rejection in vivo. However, these allospecific T-EM were unable to induce GVHD. Allospecific T-EM recipients became tolerant to alloantigen as a result of clonal deletion. Even though allospecific T-EM were able to respond to alloantigen initially, the expansion of these cells and inflammatory cytokine production during GVHD were dramatically decreased. The inability of allospecific T-EM to sustain the alloresponse may be a result of enhanced activation-induced cell death. These observations provide insight into how allospecific CD4(+) T-EM respond to alloantigen during GVHD and underscore the fundamental differences in alloresponses mediated by allospecific TEN in graft rejection and GVHD settings.

• 出版日期2012-10
• 单位上海交通大学