Panel of Reactive T Cells as a Measurement of Primed Cellular Alloimmunity in Kidney Transplant Candidates

Abstract

Pretransplantation panel reactive antibody (PRA) testing assesses posttransplantation risk for antibody-mediated graft injury. It was postulated analogously that screening for effector/memory alloreactive T cells by "panel of reactive T cells" (PRT) using IFN-␥ enzyme-linked immunosorbent spot assays would evaluate independently cellular alloimmunity in transplant candidates. Peripheral blood lymphocytes from 41 hemodialysis patients who were awaiting first renal transplants were tested against a panel of allogeneic stimulator cells. Positive assays were defined arbitrarily as >25 spots/300,000 peripheral blood lymphocytes, and positive PRT was defined as when the responder reacted to 40 or 75% (PRT-75) of the stimulators. Seventeen percent of patients were PRT-75؉, whereas 32% were PRA؉. Twelve percent of the cohort was PRT-75؉/PRA؊, and only 5% of the patients were PRA؉/PRT-75؉, indicating that T cell alloreactivity did not routinely imply B cell sensitization and vice versa. PRT-75؉ patients were more likely to be younger (<55 yr) and black. In contrast, a positive PRA was significantly associated with female gender but not race or age. Pretransplantation screening of cellular alloimmunity by enzyme-linked immunosorbent spot-based PRT detects a subset of hemodialysis patients who differ from those that are PRA؉. Preliminary correlations with posttransplantation outcome in seven recipients suggest that PRT screening has the potential to aid in risk assessment in renal transplant candidates.

Achieving Donor-Specific Hyporesponsiveness Is Associated with FOXP3+ Regulatory T Cell Recruitment in Human Renal Allograft Infiltrates

“…Mean number of IFN-␥ and IL-10 spots per 3 ϫ 10 5 responder cells were calculated by subtracting both the responder and the stimulator control wells from wells containing both the recipient and donor cells. We considered Ͼ25 spots/3 ϫ 10 5 responder cells as threshold to define a positive test (38).…”

Hemodialysis Vintage, Black Ethnicity, and Pretransplantation Antidonor Cellular Immunity in Kidney Transplant Recipients

“…Kerman et al (5) reported that, compared with white patients who were awaiting transplantation, black patients exhibited higher T lymphocyte helper:suppressor ratios and panel mixed lymphocyte reactions. In addition, Poggio et al (6) recently found a trend for higher frequencies of IFN-␥-producing T cells in black dialysis patients who were exposed to a panel of HLA antigens.…”

Biomarkers in blood for individualization of the pharmacotherapy with immunosuppressive drugs after transplantation of solid organs

“…Hricik et al have demonstrated that there is, after the transplantation, an association between the activation of T-cells by both donor-specific and nonspecific antigens and renal function [19] . To be able to also predict the immunological risk to the organ recipient prior to a post-mortem donation, a panel of donor-foreign cells with major HLA antigens has been developed [20,21] . However, the results were more convincing in the case of the living donation with donor-specific antigens [22] .…”