Inadequate Immune Regulatory Function of CD4(+)CD25(bright+)FoxP3(+) T Cells in Heart Transplant Patients who Experience Acute Cellular Rejection

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Abstract

Background. CD4(+)CD25(bright+)FoxP3(+) 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 CD4(+)CD25(bright+)FoxP3(+) 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 CD(4+)CD25(bright+) T cells and of FOxP3(+) cells within this population was comparable. Yet, CD(4+)CD25(bright+)FoxP3(+) T cells of rejectors had a higher CD127 expression than those of nonrejectors (P<0.0001). Depletion of CD4(+)CD25(bright+) 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 CD4(+)CD25(bright+) T cells only suppressed the overall antidonor proliferative response of CD25(neg/dim) responder cells of nonrejectors significantly (P=0.001). Moreover, the percentage inhibition of the response was hi p her in nonrejectors than in rejectors (P=0.02). Analyses of pretransplant samples revealed that CD4(+)CD25(bright+) T cells of rejectors already had a lower suppressive capacity than those of nonrejectors before transplantation (P=0.04). Conclusion. CD4(+)CD25(bright+)FoxP3(+) T cells of heart transplant patients who experience acute rejection had an up-regulated CD 127 expression and an inadequate regulatory function compared with those of nonrejecting patients. Our observations suggest that the function of circulating CD4(+)CD25(bright+)FoxP3(+) regulatory T cells may be pivotal for the prevention of acute cellular rejection after clinical heart transplantation.
Original languageUndefined/Unknown
Pages (from-to)1191-1200
Number of pages10
JournalTransplantation
Volume87
Issue number8
DOIs
Publication statusPublished - 2009

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