Allogeneic virus-specific T cells with HLA alloreactivity do not produce GVHD in human subjects

被引:156
作者
Melenhorst, J. Joseph [2 ]
Leen, Ann M. [1 ,3 ]
Bollard, Catherine M. [1 ,3 ]
Quigley, Maire F. [4 ,5 ]
Price, David A. [4 ,5 ]
Rooney, Cliona M. [1 ,3 ]
Brenner, Malcolm K. [1 ,3 ]
Barrett, A. John [2 ]
Heslop, Helen E. [1 ,3 ]
机构
[1] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA
[2] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA
[3] Methodist Hosp, Houston, TX 77030 USA
[4] Cardiff Univ, Sch Med, Cardiff, S Glam, Wales
[5] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
VERSUS-HOST-DISEASE; LYMPHOPROLIFERATIVE DISEASE; TRANSPLANTATION; CYTOMEGALOVIRUS; LYMPHOCYTES; RECIPIENTS; THERAPY; PREVENT; DONOR;
D O I
10.1182/blood-2010-06-289991
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Adoptive transfer of viral antigen-specific memory T cells can reconstitute antiviral immunity, but in a recent report a majority of virus-specific cytotoxic T-lymphocyte (CTL) linesshowedin vitro cross-reactivity against allo-human leukocyte antigen (HLA) molecules as measured by interferon-gamma secretion. We therefore reviewed our clinical experience with adoptive transfer of allogeneic hematopoietic stem cell transplantation donor-derived virus-specific CTLs in 153 recipients, including 73 instances where there was an HLA mismatch. There was no de novo acute graft-versus-host disease after infusion, and incidence of graft-versus-host disease reactivation was low and not significantly different in recipients of matched or mismatched CTL. However, we found that virus-specific T cell lines recognized up to 10% of a panel of 44 HLA disparate targets, indicating that virus-specific T cells can have cross-reactivity with HLA-mismatched targets in vitro. These data indicate that the adoptive transfer of partially HLA-mismatched virus-specific CTL is safe despite in vitro recognition of recipient HLA molecules. (Blood. 2010; 116(22): 4700-4702)
引用
收藏
页码:4700 / 4702
页数:3
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