Donor‐specific alloreactive T cells can be quantified from whole blood, and may predict cellular rejection after renal transplantation

• Published in: European journal of immunology Vol. 47; no. 7; pp. 1220 - 1231
• Main Authors: Fischer, Michaela, Leyking, Sarah, Schäfer, Marco, Elsäßer, Julia, Janssen, Martin, Mihm, Janine, van Bentum, Kai, Fliser, Danilo, Sester, Martina, Sester, Urban
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.07.2017
• Subjects: Adult; Alloreactive T cells; Blood; Calcineurin; Calcineurin Inhibitors - pharmacology; CCR7 protein; CD27 antigen; CD4 antigen; CD4+ T cell; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8+ T cell; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Effector cells; Female; Flow Cytometry; Graft Rejection; Health risk assessment; Histocompatibility antigen HLA; HLA Antigens - immunology; Humans; Immunologic Memory; Immunological memory; Kidney Transplantation; L-selectin; L-Selectin - genetics; L-Selectin - immunology; Lymphocytes; Lymphocytes T; Male; Memory cells; Middle Aged; Rapid flow; Receptors, CCR7 - deficiency; Receptors, CCR7 - genetics; Receptors, CCR7 - immunology; Rejection; Stimulators; Tissue Donors; Transplantation; Transplantation, Homologous; Transplants & implants; Tumor Necrosis Factor Receptor Superfamily, Member 7 - deficiency; Tumor Necrosis Factor Receptor Superfamily, Member 7 - genetics; Tumor Necrosis Factor Receptor Superfamily, Member 7 - immunology; Rejection; Transplantation; CD4+ T cell; CD8+ T cell; Alloreactive T cells
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201646826

Preformed cellular alloreactivity can exist prior to transplantation and may contribute to rejection. Here, we used a rapid flow‐cytometric whole‐blood assay to characterize the extent of alloreactive T cells among 1491 stimulatory reactions from 61 renal transplant candidates and 75 controls. The role of preformed donor‐specific alloreactive T cells in cellular rejection was prospectively analyzed in 21 renal transplant recipients. Alloreactive CD8+ T cells were more frequent than respective CD4+ T cells, and these levels were stable over time. CD8+ T cells were effector‐memory T cells largely negative for expression of CD27, CD62L, and CCR7, and were susceptible to steroid and calcineurin inhibitor inhibition. Alloreactivity was more frequent in samples with higher number of HLA mismatches. Moreover, the percentage of individuals with alloreactive T cells was higher in transplant candidates than in controls. Among transplant candidates, 5/61 exhibited alloreactive CD8+ T cells against most stimulators, 23/61 toward a limited number of stimulators, and 33/61 did not show any alloreactivity. Among 21 renal transplant recipients followed prospectively, one had donor‐specific preformed T‐cell alloreactivity. She was the only patient who developed cellular rejection posttransplantation. In conclusion, donor‐specific alloreactive T cells may be rapidly quantified from whole blood, and may predict cellular rejection after transplantation. A rapid whole blood assay was developed to quantify alloreactive CD4+ and CD8+ T cells of a recipient toward a donor based on activation and cytokine induction using flow cytometry. If determined prior to transplantation, the presence of alloreactive T cells may indicate increased risk for cellular rejection after transplantation.