NIV Congres

Background Immunological ageing of the T cell compartment is related to a decreased T cell immunity. Cytomegalovirus (CMV) infection in healthy individuals has been associated with an ageing effect on the T cell compartment and contributes to the immunedeficiency of the elderly. In this study, we investigated the effect of a primary CMV infection on T cell ageing in CMV- kidney transplant (KTx) recipients, who received a kidney from a CMV+ donor.

Methods The T cell receptor excision circle (TREC) content and % CD31⁺ naïve T cells were measured as markers for thymic output. The relative telomere length (RTL) was determined as a measure for proliferative history and immunophenotyping was used to establish the differentiation status of circulating T cells. CMV- KTx recipients receiving a kidney from a CMV+ donor (D+/R-, n=31) were compared to those receiving one from a CMV- donor (D-/R-, n=47) matching for age and immunosuppressive medication. Patients were followed prior to and at 3, 6 and 12 months post transplantation. All patients received valganciclovir during the first 6 months after transplantation.

Results At 6 months, 30% of the D+/R- KTx recipients had detectable anti-CMV IgG titers and 100% at 12 months. Four recipients developed CMV disease and were excluded from analysis. Primary CMV infection did not affect the TREC content, % CD31⁺ naïve T cells and RTL of CD4 and CD8T cells. Twelve months following KTx, absolute numbers of CD8⁺ memory T cells were increased (p<0.05) mainly as a result of a significant increase in terminally differentiated EMRA CD8⁺ T cells (p=0.03). A significant increase in the % of memory CD4⁺ as well as CD8⁺ T cells lacking CD28 expression was noticed for the D+/R- KTx recipients when comparing percentages pre to 12 months following KTx, i.e. 5.68% vs. 19.83% (p<0.05) and 32.71% vs. 60.45% (p<0.01), respectively. This increase in number of differentiated T cells was not detected in the D-/R- KTx recipients.

Conclusion Primary CMV infection in D+/R- KTx recipients does not affect thymic output or telomere length and therefore does not induce generalized immunological T cell ageing. However, CMV infection substantially increases the number of terminally differentiated CD8 and to a lesser extent CD4 T cells.

(This study was financially supported by the Dutch Kidney Foundation (KSPB.10.12))