BACKGROUND.: Allo-human leukocyte antigen (HLA) reactivity by naturally acquired viral-specific memory T cells is common. However, the effect of successful vaccination on the alloreactive memory T... Show moreBACKGROUND.: Allo-human leukocyte antigen (HLA) reactivity by naturally acquired viral-specific memory T cells is common. However, the effect of successful vaccination on the alloreactive memory T-cell repertoire is unclear. We hypothesized that vaccination could specifically induce allo-HLA-reactive memory T cells. METHODS.: A varicella-zoster virus (VZV) immediate early 62 (IE62)-specific CD8 memory T-cell clone was single cell sorted from a VZV seronegative renal transplant candidate after response to live attenuated varicella vaccination. To analyze the allo-HLA reactivity, the VZV IE62-specific T-cell clone was tested against HLA-typed target cells and target cells transfected with HLA molecules, in both cytokine production and cytotoxicity assays. RESULTS.: The varicella vaccine-induced VZV IE62-specific T-cell clone specifically produced interferon-γ when stimulated with HLA-B*55:01-expressing Epstein-Barr virus-transformed B cells and HLA-B*55:01-transfected K562 cells (single HLA antigen expressing cell line [SALs]) only. The clone also demonstrated specific cytolytic effector function against HLA-B*55:01 SALs and phytohemagglutinin blasts. Cytotoxicity assays using proximal tubular epithelial cell and human umbilical vein endothelial cell targets confirmed the kidney tissue specificity of the allo-HLA-B*55:01 reactivity, and the relevance of the cross-reactivity to clinical kidney transplantation. The results also suggest that molecular mimicry, and not bystander proliferation, is the mechanism underlying vaccine-induced alloreactivity. CONCLUSIONS.: Varicella vaccination generated a de novo alloreactive kidney cell-specific cytolytic effector memory T cell in a patient awaiting renal transplantation. Vaccination-induced alloreactivity may have important clinical implications, especially for vaccine timing and recipient monitoring. Show less
Klerk, M. de; Deijl, W.M. van der; Witvliet, M.D.; Haase-Kromwijk, B.J.J.M.; Claas, F.H.J.; Weimar, W. 2010
P>Living donor kidney exchange programs offer incompatible donor-recipient pairs the opportunity to be transplanted. To increase the number of these transplants, we examined in our actual donor... Show moreP>Living donor kidney exchange programs offer incompatible donor-recipient pairs the opportunity to be transplanted. To increase the number of these transplants, we examined in our actual donor-recipient couples how to reach the maximum number of matches by using different chain lengths. We performed 20 match procedures in which we constructed four different chain lengths: two, up to three, up to four and unlimited. The actual inflow and outflow of donor-recipient couples for each run were taken into consideration in this analysis. The total number of matched pairs increased from 148 pairs for only two-way exchanges to 168 for three-way exchanges. When a chain length of 4 was allowed five extra couples could be matched over a period of 5 years. Unlimited chain length did not significantly affect the results. The optimal chain length for living donor kidney exchange programs is 3. Longer chains with their inherent logistic burden do not lead to significantly more transplants. Show less
