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

Reactivation of cytomegalovirus (CMV) remains a serious complication after allogeneic stem cell transplantation, but the role of gamma delta T cells is undefined. We have studied the immune reconstitution of V delta 2negative (V delta 2neg) gamma delta T cells, including V delta 1 and V delta 3 subsets and V delta 2positive (V delta 2pos) gamma delta T cells in 40 patients during the first 24 months after stem cell transplantation. Significant long-term expansions of V delta 2neg but not V delta 2pos gamma delta T cells were observed during CMV reactivation early after transplantation, suggesting direct involvement of gamma delta T cells in anti-CMV immune responses. Similarly, significantly higher numbers of V delta 2neg gamma delta T cells were detected in CMV-seropositive healthy persons compared with seronegative donors; the absolute numbers of V delta 2pos cells were not significantly different. The expansion of V delta 2neg gamma delta T cells appeared to be CMV-related because it was absent in CMV-negative/ Epstein-Barr virus-positive patients. T cell receptor-delta chain determining region 3 spectratyping of V delta 2neg gamma delta T cells in healthy subjects and patients showed restricted clonality. Polyclonal V delta 2neg 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 gamma delta T cells in the immune response to CMV reactivation in transplantation recipients. (Blood. 2010;116(12):2164-2172)