Journal of Clinical and Cellular Immunology
Open Access

Abstract

Cytomegalovirus (CMV)-Reactivation Influences T-Cell Differentiation and CMV-Specific T-Cell Reconstitution after Stem Cell Transplantation

Jolanda Scherrenburg, Floor Pietersma, Ronald Jacobi, Rob Schuurman, Ellen Meijer and Debbie van Baarle

CMV-specific T cells were shown to be important for protection against CMV-disease in SCT recipients. Here we investigated specific T-cell features like effector cell differentiation and perforin-expression as well as CMV-specific T cells after SCT in relation to CMV-reactivation. To this end, CD4+ and CD8+ T-cell characteristics (differentiation, activation and functional CMV-specific immunity) of SCT patients with (n=13) or without (n=8) CMV-reactivation were analysed longitudinally by flow cytometry. CMV-specific IFNγ-production as measured by intracellular staining and proliferation as measured by CFSE dye dilution were analysed after stimulation with overlapping peptide pools of the tegument protein pp65 and immediate early antigen 1. A more differentiated phenotype, up-regulation of the activation markers CD38 and HLA-DR on CD4+ T cells and increased expression of perforin on CD8+ T cells was more frequently observed in patients with CMV-reactivation compared to patients without reactivation. Interestingly, these T-cell features were often already different early after SCT. In addition, CMV-specific CD8+ T-cell responses, both based on IFNγ-production as well as proliferation, directed against both pp65 and IE1 tended to be present more frequently in patients with CMV-reactivation compared to patients without reactivation. These data suggest that CMV-reactivation influences CMV-specific T-cell reconstitution after SCT and that early T-cell differentiation differences may be helpful in predicting viral reactivations.