Allogeneic virus-specific T cells with HLA alloreactivity do not produce GVHD in human subjects.
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) lines showed in vitro cross-reactivity against allo-human leukocyte antigen (HLA) molecules as measured by interferon-γ 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.
Melenhorst
J Joseph
JJ
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Leen
Ann M
AM
Bollard
Catherine M
CM
Quigley
Máire F
MF
Price
David A
DA
Rooney
Cliona M
CM
Brenner
Malcolm K
MK
Barrett
A John
AJ
Heslop
Helen E
HE
D019264:Adoptive Transfer; D002460:Cell Line; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation* / Q000821:virology*
D006680:HLA Antigens