Kinetics of functionally distinct T-lymphocyte subsets in heart transplant recipients after induction therapy with anti-CD25 monoclonal antibodies

Abstract

T cells are involved in the maintenance of immunocompetence and in the development of alloimmune responses in solid organ transplant recipients. The kinetics of functionally distinct T-cell subsets in peripheral blood has received little attention in the field of heart transplantation. We performed a simultaneous analysis of the maturation, activation, and regulatory profiles of T cells using 4-color flow cytometry in a study of 77 heart recipients. Induction therapy included 2 doses of anti-CD25 monoclonal antibodies (daclizumab). Lymphocyte subsets were prospectively evaluated at different times before and up to 1year after transplantation in 46 heart recipients. A separate cross-sectional study was performed in 33 heart recipients who had received a transplant more than 1year previously to evaluate abnormalities persisting in the long term. As compared with baseline values, a decrease in regulatory CD4+ T-cell percentages (CD4+CD127lowCD25highFoxP3+) was observed from day 7 to 12months after transplantation. Interestingly, T cells expressing the beta chain of IL-2 (CD122+) remained stable during the first 3months. A significant decrease in the activation status of CD4 T cells was documented from day 7 to 1year after transplantation, while the activation status of CD8+ T cells remained stable during follow-up. Compared with values for healthy controls (n=36), higher CD8+ terminally differentiated effector memory percentages (CD8+CD45RA+CCR7−) were observed from baseline up to more than 1year after transplantation. Rejection was associated with higher levels of these cells during the first 6months after transplant. We characterized the abnormalities in distinct functional T-cell subsets at different times before and after heart transplantation. Some of these abnormalities should be further investigated as biomarkers of clinical complications.