NK Cell Subsets in Renal Transplantation

Abstract

Introduction: Following kidney transplantation, the involvement of NK cells in rejection episodes or immunological tolerance is discussed controversially. The peripheral NK cell repertoire of KTx patients at 3 or 6 months post Tx was investigated in parallel to the protocol biopsy for histopathological evaluation of the graft. The alterations were correlated to the biopsy status (“unsuspicious”, T cell-mediated rejection TCMR or borderline changes) and immunosuppression, respectively. Methods: Peripheral blood lymphocytes of KTx patients (N=100) at the time of the protocol biopsy at 3 or 6 month after Tx were isolated after informed consent of the patients. In addition to the “truecount” quantification of T, B, NK cells (cell/μl), the composition of the NK cell repertoire was determined by flow cytometry for the expression of several NK receptors including KIR and CD94/NKG2. In addition to NK cells, receptor expression was also addressed in T cell subsets. In some cases, protocol biopsies and peripheral blood was available at multiple time points after Tx and, thus, changes over time and immunosuppression (CsA vs. Tac vs. mTOR inhibitors) could be defined. Results: The numbers of NK cells/μl blood differed between patients after KTx with “unsuspicious” grafts and TCMR or borderline histopathology although not at a significant level. However, the distribution of CD56bright vs. CD56dim NK cells in these patient cohorts displayed significant differences compared to healthy donors. In addition, the NK subset analyses revealed substantial differences in the numbers of KIR+ NK cells between the patient cohorts. Conclusions: In our first analyses with patients between 3 and 12 months after KTx, we could demonstrate that the numbers of NK cells in peripheral blood differs between patients with kidney grafts unsuspicious of rejection and biopsy-proven TCMR or borderline changes. In addition, a more detailed NK cell subset analysis revealed significant differences in NK subset distribution between the patient cohorts and also, for some subsets, the immunosuppressive treatment groups mTOR inhibitors, in particular. Therefore, we assume that the composition of peripheral NK cells represents an important hallmark of the immune status, rejection vs. tolerance, in kidney transplantation. (This work was funded by the IFB-Tx, DFG TRR77, A3 snd SFB738 B8 projects and the HGF Alliance Immmunotherapy).