Donor Vδ1+ γδ T cells expand after allogeneic hematopoietic stem cell transplantation and show reactivity against CMV-infected cells but not against progressing B-CLL
© Prinz et al.; licensee BioMed Central Ltd. 2013
Received: 11 February 2013
Accepted: 10 May 2013
Published: 11 May 2013
γδ T lymphocytes play an important role in immune reactions towards infections and malignancies. In particular, Vγ9–Vδ1+ T lymphocytes are thought to play protective antiviral roles in human CMV infection. Recently, Vδ1+ T lymphocytes were proposed to also have anti- B-CLL reactivity. Here we report a case of 48-year-old man who received allogeneic stem cell transplantation for progressive B-CLL. Within one year after transplantation, lymphoma relapsed despite a dramatic increase of Vδ1+ T cells in the patient’s blood. In vitro killing assays revealed activity of patient’s γδ cells against CMV target cells, but not against the relapsing lymphoma-cells. This argues for a contribution of Vδ1+ cells in the immune reaction against CMV reactivation, but does not support a strong correlation of expanded Vδ1+ T cells and favorable disease outcome in B-CLL patients.
KeywordsB-CLL Vδ1+ T lymphocytes CMV reactivation Allogeneic stem cell transplantation
Several types of T lymphocytes bearing γδ T cell receptors (TCR) are currently investigated as potential anti-cancer agents in cell-based immunotherapy. Recently, Vδ1+ T lymphocytes were shown to be cytotoxic to B-CLL-derived cell lines  and it was proposed that Vδ1+ T lymphocytes may contribute to limiting disease progression in B-CLL patients . Activated Vδ1+ T lymphocytes can produce inflammatory cytokines such as TNF-α and IFN-γ and can be cytotoxic. Both cytokine release and cytotoxicity of Vδ1+ T lymphocytes are at least in part mediated through NKG2D receptor, which recognizes the stress-induced ligands MIC-A, MIC-B, and ULBP3 on target cells. At the same time, Vδ1+ T lymphocytes are implicated in the human immune response to cytomegalovirus infection [3–7]. Patients receiving allogeneic stem cell transplantation as treatment for CLL often encounter life-threatening viral infections in the post-transplant period due to strong immunosuppression. Thereby, Vδ1+ T lymphocytes expand during post-transplant CMV reactivation and likely participate in the immune response to CMV . It has been suggested that during immune response to CMV both γδ TCR cross-reactivity and NKG2D ligands confer cross-protection against tumor cells [8–10]. Here we report a case of fulminant CMV reactivation after second allogeneic stem cell transplantation as treatment for CLL. Despite expansion of donor Vδ1+ T lymphocytes up to 25% of all circulating peripheral blood lymphocytes, no reactivity against relapsing B-CLL could be observed.
Our observations support the view that reactivity against CMV-infected cells was the driving force for Vδ1+ γδ T cell expansion in this patient. Previously, such expansion was neither observed in the stem cell donor’s peripheral blood nor in the patient’s blood before second transplantation. This argues for a contribution of Vδ1+ cells against CMV reactivation after transplantation, which is in line with recent literature . However, the expanded Vδ1+ cells were unable to kill autologous tumor cells in vitro and likely also in vivo as the lymphoma was progressing. Taken together, our findings do not match the suggested strong correlation of expanded Vδ1+ T cells and favorable disease outcome in untreated B-CLL patients .
Written informed consent was obtained from the patient for publication of this case report.
We would like to acknowledge the assistance of the Cell Sorting Core Facility of the Hannover Medical School supported in part by Braukmann-Wittenberg-Herz-Stiftung and Deutsche Forschungsgemeinschaft. We acknowledge support by Deutsche Forschungsgemeinschaft for open access publication.
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