Increase of highly differentiated CD4+CD28null T-cells is asso­ciated with a reduced risk for early acute renal transplant rejection

B. Dedeoglu, R.W.J. Meijers, M. Klepper, D.A. Hesselink, C.C. Baan, N.H.R. Litjens, M.G.H. Betjes

Chair(s): dr. Hennie G. Otten, medisch immunoloog, UMC Utrecht & dr. Laura B. Bungener, medisch immunoloog, UMC Groningen

Thursday 10 march 2016

9:10 - 9:20h at Zaal 1 & 2

Categories: Parallelsessie (basaal)

Parallel session: Parallelsessie VII - Basaal immunologie

End-stage renal disease patients have a dysfunctional, prematurely aged peripheral T-cell system. Here we hypothesized that the degree of premature T-cell ageing before kidney transplantation predicts the risk for early acute allograft rejection (EAR).

222 living donor kidney transplant recipients were prospectively analyzed. EAR was defined as biopsy proven acute allograft rejection within 3 months after kidney transplantation. The differentiation status of circulating T cells, the relative telomere length and the number of recent thymic emigrants (RTE; defined as CD31+ naive T cells) were determined as T-cell ageing parameters.

Of the 222 patients analyzed, 30 (14%) developed an EAR. The donor age and the historical panel reactive antibody score were significantly higher (p=0.024 and p=0.039 respectively) and the number of related donor kidney transplantation was significantly lower (p=0.018) in the EAR group. EAR-patients showed lower CD4+CD28null T-cell numbers (p<0.01) and the same trend was observed for CD8+CD28null T-cell numbers (p=0.08). No differences regarding the other ageing parameters were found. A multivariate Cox regression analysis showed that higher CD4+CD28null T-cell numbers was associated with a lower risk for EAR (HR: 0.65, p=0.028). A Kaplan-Meier analysis showed that patients with high numbers of CD4+CD28null T-cells (>36.67 cells/µl) had a significantly higher EAR free survival than patients with intermediate (4.33–36.67 cells/µl) and low (<4.33 cells/µl) numbers of these cells (p=0.008 and p=0.009 respectively). In vitro, a significant lower percentage of alloreactive T cells was observed within CD28null T cells (p<0.001).

Immunological ageing-related expansion of highly differentiated CD28null T cells is associated with a lower risk for EAR.