PMC7868410_01
Control of cytomegalovirus (CMV) infection in a renal transplant recipient with a UL54 DNA polymerase gene mutation A834P. (A) Time course of CMV-DNAemia in relation to antiviral therapy with ganciclovir (i.v. and valganciclovir, shaded areas, for more information see text), modulation of immunosuppression from mycophenolate mofetil (myf) to an mTOR inhibitor and from tacrolimus (Tac) to cyclosporine A (CyA). In addition, the patient received CMV-specific i.v. immunoglobulins (IVIG). (B) Time course of absolute numbers of CMV-specific CD4 and CD8 T cells (black symbols) determined by flow-cytometry after specific stimulation with a CMV lysate and CMV peptides. In addition the expression level of CTLA-4 was determined [denoted as MFI (median fluorescence intensity)]. (C) Original data of CMV-specific CD4 and CD8 T cells determined over time (upper panels). The bottom panels show the time course in CD4 and CD8 T cells polyclonally stimulated with Staphylococcus aureus Enterotoxin B (SEB). Specifically activated T cells were characterized by expression of CD69 and interferon gamma (IFNgamma).
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One week after stopping prophylaxis, asymptomatic CMV replication was detected at a level of 57,200 IU/ml (week 14,  Figure 1A ). In addition, the patient received high dose CMV-specific IVIG for 8 consecutive days (10.000 units per day,  Figure 1A ). CMV-IVIG treatment was continued with 10.000 units once a week ( Figure 1A ). Interestingly, after discharge from hospital (week 25), CMV-specific CD4 and CD8 T cells were detectable ( Figures 1B, C ). However, consistent with high viral load, absolute counts/microl were very low, and their phenotypical and cytokine expression pattern showed typical signs of functional anergy characterized by high expression of CTLA-4 and limited ability to produce cytokines ( Figure 1B  and data not shown). CMV-specific T-cell numbers had remained stable. Consistent with successful viral control, CTLA-4 expression and cytokine profile of CMV-specific T cells had normalized over time ( Figures 1B, C ).