The role of Vδ2-negative γδ T cells during cytomegalovirus reactivation in recipients of allogeneic stem cell transplantation

• Published in: Blood Vol. 116; no. 12; pp. 2164 - 2172
• Main Authors: Knight, Andrea, Madrigal, Alejandro J., Grace, Sarah, Sivakumaran, Janani, Kottaridis, Panagiotis, Mackinnon, Stephen, Travers, Paul J., Lowdell, Mark W.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 23.09.2010; Americain Society of Hematology
• Subjects: Adolescent; Adult; Biological and medical sciences; Cell Proliferation; Child; Cytomegalovirus - physiology; Cytomegalovirus Infections - etiology; Cytomegalovirus Infections - immunology; Female; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Infectious diseases; Male; Medical sciences; Middle Aged; Receptors, Antigen, T-Cell, gamma-delta - immunology; T-Lymphocyte Subsets - immunology; Transplantation, Homologous; Viral diseases; Virus Activation; Young Adult; Cytomegalovirus; Reactivation; Hematology; γ/δ T cell receptor; Herpesviridae; Stem cell; Hematopoietic cell; Homograft; Recipient; Betaherpesvirinae; Vδ2 T cell receptor; Infection; Virus; Viral disease; Graft
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2010-01-255166

Reactivation of cytomegalovirus (CMV) remains a serious complication after allogeneic stem cell transplantation, but the role of γδ T cells is undefined. We have studied the immune reconstitution of Vδ2negative (Vδ2neg) γδ T cells, including Vδ1 and Vδ3 subsets and Vδ2positive (Vδ2pos) γδ T cells in 40 patients during the first 24 months after stem cell transplantation. Significant long-term expansions of Vδ2neg but not Vδ2pos γδ T cells were observed during CMV reactivation early after transplantation, suggesting direct involvement of γδ T cells in anti-CMV immune responses. Similarly, significantly higher numbers of Vδ2neg γδ T cells were detected in CMV-seropositive healthy persons compared with seronegative donors; the absolute numbers of Vδ2pos cells were not significantly different. The expansion of Vδ2neg γδ T cells appeared to be CMV-related because it was absent in CMV-negative/Epstein-Barr virus-positive patients. T-cell receptor-δ chain determining region 3 spectratyping of Vδ2neg γδ T cells in healthy subjects and patients showed restricted clonality. Polyclonal Vδ2neg cell lines generated from CMV-seropositive healthy donors and from a recipient of a graft from a CMV-positive donor lysed CMV-infected targets in all cases. Our study shows new evidence for role of γδ T cells in the immune response to CMV reactivation in transplantation recipients.