Reconstitution and Phenotype of Tregs in CMV Reactivating Patients Following Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

In experimental and clinical settings Tregs prevent graft-versus-host disease (GvHD) by inhibiting the proliferation and function of conventional T cells (Tconv). The suppressive potency of Tregs might also lead to the inhibition of protective antiviral T cell responses. As the control of CMV reactivation is important to improve the clinical outcome in allogeneic HSCT, we analyzed the Treg reconstitution in CMV reactivating patients with and without GvHD (n=47) in the first 6 months following transplantation. Most importantly, CMV reactivation does not correlate with the numerical reconstitution of CD4⁺CD25^highCD127⁻ Tregs. During CMV reactivation the proportion of Tregs within the CD4⁺ T cell population decreased significantly independent of GvHD manifestation. A comprehensive FACS analysis was performed in order to characterize the phenotype of Tregs and Tconv cells in greater detail for activation, co-stimulation, proliferation, suppressive function and migratory capability. Interestingly, Tregs of patients with CMV reactivation showed a significantly higher CXCR3 expression. CD4⁺ Tconv cells expressed significantly higher protein levels of the proliferation marker Ki67 correlating with a numerical increase of CD4⁺ T cells. Our results indicate that Tregs are not inhibiting pathogen clearance by Tconv following HSCT, which is of high relevance for future Treg cell-based clinical trials in allogeneic HSCT.

• Regulatory T cells
• CMV infection
• Stem cell transplantation
• Phenotype

ACKNOWLEDGMENT

This work was supported by a grant from the German Federal Ministry of Education and Research (reference number: 01EO0802). We thank the clinical co-workers from the BMT unit for support in probe sampling and Matthias Ballmeier and his co-workers for FACS based cell sorting.

Declaration of Interests

The author(s) declare having no competing interests. The authors are responsible for the content and the writing of this paper.

Notes

Authors Velaga and Ukena contributed equally to this article.