Current address: Children’s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
Decreases in circulating CD4+CD25hiFOXP3+ cells and increases in intragraft FOXP3+ cells accompany allograft rejection in pediatric liver allograft recipients
Article first published online: 10 MAR 2008
© 2008 Wiley Periodicals, Inc.
Volume 13, Issue 1, pages 70–80, February 2009
How to Cite
Stenard, F., Nguyen, C., Cox, K., Kambham, N., Umetsu, D. T., Krams, S. M., Esquivel, C. O. and Martinez, O. M. (2009), Decreases in circulating CD4+CD25hiFOXP3+ cells and increases in intragraft FOXP3+ cells accompany allograft rejection in pediatric liver allograft recipients. Pediatric Transplantation, 13: 70–80. doi: 10.1111/j.1399-3046.2008.00917.x
- Issue published online: 6 JAN 2009
- Article first published online: 10 MAR 2008
- Accepted for publication 9 January 2008
- T regulatory cells;
- acute rejection;
- T lymphocytes;
- immune responses;
- liver transplantation
Abstract: We examined CD4+CD25hiFOXP3+ cells Treg in children following liver transplantation and determined the relationship between Treg cell levels in the blood and in the graft. Peripheral blood was obtained from pediatric liver transplant patients at sequential time points: pre-transplant, one month, 3–4 months, 6–7 months, and 11–12 months post-transplant. PBMC were isolated, labeled for CD4, CD25 and FOXP3 expression and analyzed by flow cytometry for CD4+CD25hiFOXP3+ cells. Sorted CD4+CD25hi cells were assessed for functional activity. Pretransplant blood levels of CD4+CD25hiFOXP3+ Treg cells were not significantly different from post-transplant blood levels of CD4+CD25hiFOXP3+ Treg cells. However, the blood levels of CD4+CD25hiFOXP3+ Treg cells were significantly decreased during acute rejection compared with levels when graft function was stable. Immunohistochemistry revealed that FOXP3+ cells were increased in the portal region of livers with histopathologic evidence of acute graft rejection compared with livers without evidence of rejection and were localized primarily within the inflammatory infiltrate. These data indicate that Treg cells are found at the site of allograft rejection and may play a role in regulation of alloreactivity. Moreover, monitoring peripheral CD4+CD25hiFOXP3+ Treg cell levels may be useful in improving the post-transplant management of pediatric liver allograft recipients.