A primary infection with cytomegalovirus (CMV) is one of the major threats following transplantation of a CMV-IgG-seropositive donor organ into a CMV-IgG-seronegative individual. Therefore, prophylactic treatment with valganciclovir is given in these individuals. However, CMV-specific T-cell immunity may exist without measurable anti-CMV IgG. The frequency and clinical relevance of solitary CMV-specific T-cell immunity is not known. The aim of this study is to assess the frequency of solitary CMV-specific T cells in a cohort of CMV-IgG-seronegative individuals and the clinical relevance with respect to CMV-infection following transplantation.

In a cohort of 28 CMV-IgG-seronegative and 14 CMV-IgG-seropositive individuals, CMV-specific cytokine-producing and proliferating T cells were assessed prior to transplantation using the CD137 multi-parameter assay and CFSE-dilution, respectively. CMV-specific humoral immunity was evaluated using the B-cell ELISPOT assay.

In 46% of CMV IgG-seronegative individuals CMV-specific CD137⁺IFN-γ-producing CD4⁺ T cells were detected above background (median values amounted to 0.01% versus 0.58% in CMV-IgG-seropositive individuals). CMV-specific proliferating CD4⁺ T cells were detected above background in 55% of the CMV-IgG-seronegative individuals (median values amounted to 0.4% versus 6.34% in CMV-IgG- seropositive individuals). CMV-specific IgG-producing antibody secreting cells (ASC) were barely detected in CMV-IgG-seronegative individuals (median values amounted to 3/10⁵ cells versus 48/10⁵ cells in CMV-IgG-seropositive individuals). However, a positive association was observed for CMV-specific CD137⁺IFN-γ-producing CD4⁺ T cells and CMV-specific IgG ASC (Rs=0.52, P<0.05). In 46% of CMV IgG-seronegative individuals a CMV-viremia developed following transplantation. CMV-specific CD137⁺IFN-γ-producing CD4⁺ T cells were associated with protection from a CMV-viremia following transplantation, i.e. positive responses were detected in 10/15 non-viremic versus 3/13 viremic recipients of a kidney transplant from a CMV-IgG-seropositive donor (P=0.02).

A solitary CMV-specific T-cell response without detectable anti-CMV antibodies is frequent and clinically relevant as it yields significant protection to infection following transplantation with a kidney from a CMV-IgG-seropositive donor.

CITATION INFORMATION: Litjens N, Huang L, Dedeoglu B, Meijers R, Betjes M. CMV-Specific CD4⁺ T Cells in CMV-IgG-Seronegative Individuals Protect from CMV Viremia Following Transplantation with a CMV-Seropositive Donor Kidney. Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress