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Allospecific memory T cells are a barrier against long-term graft survival. Production of multiple cytokines by a single T cell is considered a sign of an active ongoing immune response, the presence of these polyfunctional cells has not been addressed in transplanted patients accordingly to graft outcome. Memory phenotype, based on the expression of CD45RO and CD27, and polyfunctional T cells were evaluated in long-term graft survival patients (LTS), short-term survival patients (STS), chronic rejection patients (ChrRx), dialysis patients (DIAL) and healthy controls (Ctrls). Memory T cells were quantified ex vivo, after allogeneic and anti-CD3 plus anti-CD28 stimulation, in cells proliferating or not to these stimuli. The percentages of cells producing IFNγ, IL-2 and/or TNFα after allogeneic stimulation and the memory phenotype of single cytokine producing cells were evaluated. Ex vivo CD8+CD45RO-CD27- effector cells were decreased in transplanted patients compared to non-transplanted individuals. After allogeneic stimulation, CD4+CD45RO+CD27+, central memory cells in LTS and CD4+CD45RO-CD27- effector cells in Dial were augmented compared to Ctrls and ChrRx, and CD8+CD45RO-CD27- effector cells were increased in ChrRx. There were no differences in the percentage of single cytokine producing cells among the groups. IFNγ+TNFα+CD4 and CD8 cells were detected in Ctrls, STS and ChrRx and no cells positive for the three cytokines were found. The phenotype of cytokine producing cells was mainly effector memory. Interestingly, in LTS there was an increase in effector cells producing IFNγ and IL-2. Changes in subpopulation distribution in patients with different outcomes may be a reflection of the graft acceptance or rejection status., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Transplant patients with long-term graft survival (LTS) may have developed mechanisms that prevent rejection and allow graft function under low or no immunosuppressive therapy. In murine models, T cell tolerance is associated with alterations in the expression/activation of proteins involved in T cell signaling. These alterations have not been reported in transplanted patients with different outcomes. This study aimed to evaluate calcium mobilization, the phosphorylation of different proteins involved in T cell signaling and the expression of molecules associated with anergy, in T cells from kidney transplant patients. No differences were observed in calcium mobilization, although transplanted patients had a tendency toward augmented calcium flux. Chronic rejection patients (ChrRx) displayed lower Lck basal phosphorylation levels compared with LTS patients, and the phosphorylation profile of proteins evaluated was different. Among the groups, phosphorylation of Zap-70 was higher in LTS patients compared with ChrRx, and LAT phosphorylation was lower in LTS and ChrRx patients compared with healthy controls. The expression of molecules related to the anergic phenotype was similar among the study groups. Results suggest that phosphorylation patterns, rather than phosphorylation levels, may correlate with transplant outcome and that anergy may not be the main mechanism mediating LTS., (© 2012 John Wiley & Sons A/S.)