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

• Published in: Blood Vol. 116; no. 22; pp. 4700 - 4702
• Main Authors: Melenhorst, J. Joseph, Leen, Ann M., Bollard, Catherine M., Quigley, Máire F., Price, David A., Rooney, Cliona M., Brenner, Malcolm K., Barrett, A. John, Heslop, Helen E.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 25.11.2010; Americain Society of Hematology; American Society of Hematology
• Series: Transplantation
• Subjects: Adoptive Transfer; Biological and medical sciences; Cell Line; Graft vs Host Disease - etiology; Graft vs Host Disease - immunology; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Transplantation; HLA Antigens - immunology; Humans; Medical sciences; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - transplantation; T-Lymphocytes, Cytotoxic - virology; Transplantation; Human; Virus; Immunopathology; Graft versus host disease; HLA-System; Hematology; Stem cell; Major histocompatibility system; T-Lymphocyte; Hematopoietic cell
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2010-06-289991

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.