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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.)