ACTIVATION AND ROLE OF T REGULATORY CELLS

A. Lehnhardt¹, F. Dunst¹, M. Van husen¹, D.E. Müller-wiefel¹, M. Koch², M.J. Kemper^1
1Pediatric Nephrology, University Medical Center Hamburg-Eppendorf, Hamburg/GERMANY, ²Hepatobiliäre Chirurgie Und Transplantation, University Medical Hospital Hamburg-Eppendorf, Hamburg/GERMANY

Body: Introduction: Standard immunosuppressive regimes after pediatric kidney transplantation (PKTx) mainly target T-cells. Only little is known about its influence on FoxP3+ regulatory T-cells (T-Regs) and even less about B-cell immunity and B-cell activating factor (BAFF, BlyS) and its receptor BAFF-R (BR3), which are integral for B-cell activation, survival, and homeostasis. Aim of our study was a cross-sectional analysis of specific markers of regulatory T-cells and B-cell regulation in a cohort of children after renal transplantation. Patients and Methods: 34 children (10 girls) with a median age of 13.3 years (range 3-17), were studied 4.3 (range 1-12.4) years after PKTx. Most patients received immunosuppressive triple therapy with steroids (n=27), calcineurin inhibitors (n=31) and mycophenolic acid (n=27). 12 age matched healthy children served a s controls. FACS analysis for lymphocyte surface antigens CD3, CD4, CD8, CD19, CD25b and BAFF-R as well as intracellular FoxP3 was performed. Serum-BAFF was measured with commercially available ELISA. Results: While absolute numbers (mean ± SE) of lymphocytes as well as relative numbers of CD8+ T-cells and CD4+CD25+FoxP3+ regulatory T-cells (1.28±0.68 vs 1.18±0.70%) were comparable, the frequency of CD3+ (78.8 ± 9.4 vs 69.0 ± 6.1 %) and CD4+ T-cells (49.2±9.4 vs 40.7±5.2%) were increased compared to healthy controls (both p<0,001). There was a significant decrease in CD19+ B-cells (10.1±3.7 vs 16.6±5.3%, p=0.001). Serum-BAFF was increased in patients (1375±428 vs 846±146 pg/ml, p<0.001), whereas differences in median BAFF-R expression (MFI) on CD19+ cells were not statistically significant (414, range 108 -1683 vs 501, range 280 -1128). In contrast to murine data no BAFF-R expression was seen on T-cells. Within the group of renal transplant patients serum BAFF was inversely correlated with BAFF-R expression (p<0.03, r=0.395) and calculated GFR (p<0.04, r=0.355). The relative number of T-Regs was correlated with BAFF-R expression on CD19+ B-cells (p=0.017, r=0.407) and time after PKTx (p=0.003, r=0.499). Conclusion: Distinct changes in lymphocyte subpopulations including regulatory T-cells and BAFF/BAFF-R are present after PKTx compared to healthy controls. High BAFF levels may result in chronic allograft injury, possibly by promoting survival of alloreactive B-cells. The increase of T-Regs together with higher BAFF-R expression on B cells during follow-up may be indicators of partial tolerance. Future studies in the regulation of T- and B-cell immunity after PKTx are urgent and may allow for a more individual tailoring of immunosuppression.

Disclosure: All authors have declared no conflicts of interest.