Allo-HLA reactivity of virus-specific memory T cells is common

作者：Amir Avital L; D'Orsogna Lloyd J A; Roelen Dave L; van Loenen Marleen M; Hagedoorn Renate S; de Boer Renate; van der Hoorn Menno A W G; Kester Michel G D; Doxiadis Ilias I N; Falkenburg J H Frederik; Claas Frans H J; Heemskerk Mirjam H M^*

来源：Blood, 2010, 115(15): 3146-3157.

DOI：10.1182/blood-2009-07-234906

Graft-versus-host disease and graft rejection are major complications of allogeneic HLA-mismatched stem cell transplantation or organ transplantation that are caused by alloreactive T cells. Because a range of acute viral infections have been linked to initiating these complications, we hypothesized that the cross-reactive potential of virus-specific memory T cells to allogeneic (allo) HLA molecules may be able to mediate these complications. To analyze the allo-HLA reactivity, T cells specific for Epstein-Barr virus, cytomegalovirus, varicella zoster virus, and influenza virus were tested against a panel of HLA-typed target cells, and target cells transduced with single HLA molecules. Eighty percent of T-cell lines and 45% of virus-specific T-cell clones were shown to cross-react against allo-HLA molecules. The cross-reactivity of the CD8 and CD4 T-cell clones was directed primarily against HLA class I and II, respectively. However, a restricted number of CD8 T cells exhibited cross-reactivity to HLA class II. T-cell receptor (TCR) gene transfer confirmed that allo-HLA reactivity and virus specificity were mediated via the same TCR. These results demonstrate that a substantial proportion of virus-specific T cells exert allo-HLA reactivity, which may have important clinical implications in transplantation settings as well as adoptive transfer of third-party virus-specific T cells. (Blood. 2010;115(15):3146-3157)

• 出版日期2010-4-15