Background/Aims: Cytomegalovirus infection is a significant cause of morbidity in transplant patients and has been associated with allograft rejection. In this study frequencies of IFNg-producing T cells following ex-vivo stimulation with protein-spanning peptide pools for CMV proteins pp65 and IE1 as well as donor-reactive T cell frequencies were serially determined during the first 6 months after renal transplantation (Tx) to analyse the relation of CMV specific T cells, virus control and alloimmunity. Patients: 64 kidney transplant recipients were included. Immunosuppression generally consisted of anti- IL-2R mAb, calcineurin inhibitor, MMF and steroids. 2 presensitized patients received an induction by 2x low dose OKT-3, anti-TNF mAb, anti-CD20 mAb and 5x plasmapheresis. 8 Patients received FTY-720, cyclosporine and steroids. Methods: PBMCs from renal transplant recipients were analysed in a computer-assisted ELISPOT assay before and at multiple times (mean 5) post-transplantation for IFN-y-producing T cells following in-vitro stimulation for 24 hrs by irradiated donor cells and pools of overlapping peptides covering the complete CMV IE-1 and pp65 proteins. Results: CMV seropositive transplant recipients had significantly hightened IE-1 and pp65 specific T cell frequencies compared to seronegative individuals. Patients with evidence of CMV antigenemia or DNAemia could not be discriminated based on CMV- and donor-reactive T cells or serum creatinine. However, recipients of seropositive grafts with low IE1 response showed a tendency towards more frequent CMV infection. CMV disease was observed in only 3/64 individuals. 2 had no detectable IE1- or pp65-T cell response, the third presented with a dominant pp65 response. Interestingly, IE1-specific T cells correlated inversely with early post-Tx donor-reactive T cell frequencies during weeks 1-2 post-Tx. Most importantly, IE1-specific T cell frequencies correlated inversely with serum creatinine at 6 and 12 months at several times post-Tx. In patients without acute rejection, even pretransplant IE-1 specific T cells correlated inversely with 6 and 12 months creatinine. Conclusion: These data suggest subclinical control of CMV infection by IE-1 specific T cells and subsequently less graft injury by (CMV-induced) alloimmunity.
Full conference title:
16th European Congress of Clinical Microbiology and Infectious Diseases
- ECCMID 16th (2006)