Immunosuppression affects circulating follicular regulatory T cells in kidney transplant recipients

C.C. Baan, Q. Niu, A. Mendoza Rojas, M. Dieterich, T. van Gelder, D.A. Hesselink, N.M. van Besouw

Wednesday 4 march 2020

15:20 - 15:30h at Joep Nicolas zaal

Parallel session: Parallel sessie IV – Basale abstracts

Background: FoxP3⁺ follicular regulatory T cells (Tfr) have been identified as the cell population controlling T follicular helper (Tfh) cells and B cells that are involved in effector immune responses against transplanted tissue.

Methods: To understand the biology of Tfr cells in kidney transplant patients receiving tacrolimus based immunosuppression, we measured circulating (c)Tfh and cTfr cells in peripheral blood at 5-7 years after transplantation by flow cytometry. Of this cohort 26% (58/227) had been treated for rejection of which 16% was diagnosed as T cell mediated rejection (TCMR), 7% as chronic (c)ABMR and 3% as mixed rejection. Median time after anti-rejection therapy was 4.9 years (range 0.4–7 years). Age and gender matched heathy individuals served as controls.

Results: While the absolute numbers of cTfh cells was comparable between kidney recipients and healthy controls, the numbers for cTfr cells were 46% lower in immunosuppressed recipients (median 8.8×10⁶/L vs. 16.2×10⁶/L, p<0.001). More importantly, the ratio of Tfr/Tfh was decreased, indicating a disruption of the balance between cTfh and cTfr cells. This shifted balance was observed for both non-rejectors and rejectors. Previous pulse steroid anti-rejection therapy led to 29% (median) fewer cTfr cells, IvIG to a 40% and alemtuzumab therapy to 85% (ps=0.13, p=0.04).

Conclusions: Our work shows that anti-rejection therapy significantly affects the number of cTfr cells in kidney transplant recipients. The observed profound, long lasting effects by these agents might dysregulate cTfr functions.