Ectopic lymphoid structures are present in type I T-cell mediated kidney transplant rejection

---

K. de Leur, M.C. Clahsen-van Groningen, G.N. de Graav, D.A. Hesselink, J.N.M Samsom, C.C. Baan, K. Boer

Chair(s): Dr. Junior M. Lardy

Thursday 9 march 2017

13:00 - 13:15h

Categories: Poster - Basaal

Parallel session: Postersessie XV - Basaal 3

---

In renal transplantation, many allograft recipients develop donor-specific antibodies associated with an increased risk for graft rejection. Current immunosuppressive agents are principally aimed at T-cell-mediated alloimmunity, underestimating humoral effectors. Antibody responses are mainly mediated by BCL6+ T follicular helper (Tfh)-cells that activate B-cells predominantly via interleukin-21 (IL-21). Whether this reaction appears in the allograft is still being debated. Here, we investigated if ectopic lymphoid structures (ELSs) are present in T cell mediated rejection (type I and II) and antibody-mediated rejection after renal transplantation.

Fifteen renal transplant biopsies were studied. Primary diagnosis were C4d+ antibody-mediated rejection (ABMR, n=5), T-cell mediated rejection type I (TCMRI, n=5), and T-cell mediated rejection type II (TCMRII, n=5). FFPE sections were stained for T-cells (CD3), B-cells (CD20), and follicular dendritic cells (FDCs, CD23). In addition, double immunofluorescent stainings for IL-21 and BCL6 were performed. Slides were analyzed for the presence and composition of infiltrate.

In all 15 biopsies, infiltrates of CD3+ T cells were detected. In TCMRI, CD20+ B-cells formed aggregates surrounded by T-cells in the tubulo-interstitial compartment. In these aggregates CD23+ FDCs were detected, suggesting the presence ELSs. In contrast, ABMR and TCMRII showed diffuse spread of T cells and B cells and no CD23+ cell aggregates. IL-21 was present in all biopsies, however, co-localization with BCL6 was predominantly observed in TCMRI biopsies.

Nodal lymphoid proliferations with FDC networks and BCL6+IL-21+ cells are mainly found in TCMRI and may suggest a pivotal role for Tfh cell – B cell interaction.