Inadequate immune regulatory function of CD4+CD25bright+FoxP3+ T cells in heart transplant patients who experience acute cellular rejection
BACKGROUND.: CD4CD25FoxP3 regulatory T cells are suppressors of antigen-activated immune reactivity. Here, we assessed the clinically relevant role of these cells in the control of immune responses directed to a transplanted heart. METHODS.: We investigated the phenotype and function of peripheral CD4CD25FoxP3 T cells in heart transplant patients free from acute rejections (n=9) and in rejectors (n=12) before and during acute cellular rejection. RESULTS.: Between rejectors and nonrejectors, the proportion of CD4CD25 T cells and of FoxP3 cells within this population was comparable. Yet, CD4CD25FoxP3 T cells of rejectors had a higher CD127 expression than those of nonrejectors (P=0.0001). Depletion of CD4CD25 T cells from peripheral blood mononuclear cells increased the antidonor proliferative response of both nonrejectors (P≤0.0005) and rejectors (P≤0.03). In rejectors, however, only a 2-fold increase was measured, whereas the nonrejectors' response became 14 times higher (P=0.002). Reconstitution of CD4CD25 T cells only suppressed the overall antidonor proliferative response of CD25 responder cells of nonrejectors significantly (P=0.001). Moreover, the percentage inhibition of the response was higher in nonrejectors than in rejectors (P=0.02). Analyses of pretransplant samples revealed that CD4CD25 T cells of rejectors already had a lower suppressive capacity than those of nonrejectors before transplantation (P=0.04). CONCLUSION.: CD4CD25FoxP3 T cells of heart transplant patients who experience acute rejection had an up-regulated CD127 expression and an inadequate regulatory function compared with those of nonrejecting patients. Our observations suggest that the function of circulating CD4CD25FoxP3 regulatory T cells may be pivotal for the prevention of acute cellular rejection after clinical heart transplantation.
|Keywords||Allogeneic reactivity, CD4 antigen, FOXP3 protein, Heart transplant patients, Peripheral blood, Regulatory T cells, T lymphocyte, acute disease, adult, article, female, forkhead transcription factor, genetics, graft rejection, heart transplantation, human, immunology, interleukin 2 receptor alpha, leukocyte antigen, lymphocyte activation, male, middle aged, mixed lymphocyte culture, regulatory T lymphocyte|
|Persistent URL||dx.doi.org/10.1097/TP.0b013e31819ec2fb, hdl.handle.net/1765/16400|
Dijke, I.E., Korevaar, S.S., Caliskan, K., Balk, A.H.M.M., Maat, A.W.P.M., Weimar, W., & Baan, C.C.. (2009). Inadequate immune regulatory function of CD4+CD25bright+FoxP3+ T cells in heart transplant patients who experience acute cellular rejection. Transplantation, 87(8), 1191–1200. doi:10.1097/TP.0b013e31819ec2fb