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

Background:
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).

Methods:
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.

Results:
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).

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