Anti-CD25 treatment and FOXP3-positive regulatory T cells in heart transplantation

G. Vlad; E. K. Ho; E. R. Vasilescu; J. Fan; Z. Liu; J. W. Cai; Z. Jin; E. Burke; M. Deng; M. Cadeiras; R. Cortesini; S. Itescu; C. Marboe; D. Mancini; N. Suciu-Foca

doi:10.1016/j.trim.2007.03.001

Anti-CD25 treatment and FOXP3-positive regulatory T cells in heart transplantation

G. Vlad, E. K. Ho, E. R. Vasilescu, J. Fan, Z. Liu, J. W. Cai, Z. Jin, E. Burke, M. Deng, M. Cadeiras, R. Cortesini, S. Itescu, C. Marboe, D. Mancini, N. Suciu-Foca

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

Abstract

The interleukin-2 receptor alpha chain (IL-2Ra, CD25) plays a major part in shaping the dynamics of T cell populations following immune activation, due to its role in T cell proliferation and survival. Strategies to blunt the effector responses in transplantation have been developed by devising pharmaceutical agents to block the IL-2 pathways. However, such strategies could adversely affect the CD25⁺FOXP3⁺T regulatory (T reg) populations which also rely on intereukin-2 signaling for survival. The present study shows that a cohort of heart allograft recipients treated with Daclizumab (a humanized anti-CD25 antibody) display FOXP3 expression patterns consistent with functional T regulatory cell populations. High levels of FOXP3 were observed to correlate with lower incidence of and recovery from acute rejection, as well as lower levels of anti-donor HLA antibody production. Therefore, T reg populations appear fully functional in patients treated with Daclizumab, even when 5 doses were administered. By comparison, patients treated with fewer doses or no Daclizumab had a higher incidence of acute rejection, antibody production and graft failure. Therefore, our data indicates that Daclizumab treatment does not interfere with the generation of regulatory T cells and has a beneficial effect on heart allograft survival.

Original language	English
Pages (from-to)	13-21
Number of pages	9
Journal	Transplant Immunology
Volume	18
Issue number	1
DOIs	https://doi.org/10.1016/j.trim.2007.03.001
State	Published - Jul 2007
Externally published	Yes

Keywords

Daclizumab
FOXP3
Heart transplantation
Rejection
T regulatory cells

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10.1016/j.trim.2007.03.001

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title = "Anti-CD25 treatment and FOXP3-positive regulatory T cells in heart transplantation",

abstract = "The interleukin-2 receptor alpha chain (IL-2Ra, CD25) plays a major part in shaping the dynamics of T cell populations following immune activation, due to its role in T cell proliferation and survival. Strategies to blunt the effector responses in transplantation have been developed by devising pharmaceutical agents to block the IL-2 pathways. However, such strategies could adversely affect the CD25+FOXP3+T regulatory (T reg) populations which also rely on intereukin-2 signaling for survival. The present study shows that a cohort of heart allograft recipients treated with Daclizumab (a humanized anti-CD25 antibody) display FOXP3 expression patterns consistent with functional T regulatory cell populations. High levels of FOXP3 were observed to correlate with lower incidence of and recovery from acute rejection, as well as lower levels of anti-donor HLA antibody production. Therefore, T reg populations appear fully functional in patients treated with Daclizumab, even when 5 doses were administered. By comparison, patients treated with fewer doses or no Daclizumab had a higher incidence of acute rejection, antibody production and graft failure. Therefore, our data indicates that Daclizumab treatment does not interfere with the generation of regulatory T cells and has a beneficial effect on heart allograft survival.",

keywords = "Daclizumab, FOXP3, Heart transplantation, Rejection, T regulatory cells",

author = "G. Vlad and Ho, {E. K.} and Vasilescu, {E. R.} and J. Fan and Z. Liu and Cai, {J. W.} and Z. Jin and E. Burke and M. Deng and M. Cadeiras and R. Cortesini and S. Itescu and C. Marboe and D. Mancini and N. Suciu-Foca",

note = "Funding Information: This work was supported by RO1 AI55234-04 and the Interuniversitary Organ Transplantation Consortium, Rome, Italy.",

year = "2007",

month = jul,

doi = "10.1016/j.trim.2007.03.001",

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T1 - Anti-CD25 treatment and FOXP3-positive regulatory T cells in heart transplantation

AU - Vlad, G.

AU - Ho, E. K.

AU - Vasilescu, E. R.

AU - Fan, J.

AU - Liu, Z.

AU - Cai, J. W.

AU - Jin, Z.

AU - Burke, E.

AU - Deng, M.

AU - Cadeiras, M.

AU - Cortesini, R.

AU - Itescu, S.

AU - Marboe, C.

AU - Mancini, D.

AU - Suciu-Foca, N.

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PY - 2007/7

Y1 - 2007/7

N2 - The interleukin-2 receptor alpha chain (IL-2Ra, CD25) plays a major part in shaping the dynamics of T cell populations following immune activation, due to its role in T cell proliferation and survival. Strategies to blunt the effector responses in transplantation have been developed by devising pharmaceutical agents to block the IL-2 pathways. However, such strategies could adversely affect the CD25+FOXP3+T regulatory (T reg) populations which also rely on intereukin-2 signaling for survival. The present study shows that a cohort of heart allograft recipients treated with Daclizumab (a humanized anti-CD25 antibody) display FOXP3 expression patterns consistent with functional T regulatory cell populations. High levels of FOXP3 were observed to correlate with lower incidence of and recovery from acute rejection, as well as lower levels of anti-donor HLA antibody production. Therefore, T reg populations appear fully functional in patients treated with Daclizumab, even when 5 doses were administered. By comparison, patients treated with fewer doses or no Daclizumab had a higher incidence of acute rejection, antibody production and graft failure. Therefore, our data indicates that Daclizumab treatment does not interfere with the generation of regulatory T cells and has a beneficial effect on heart allograft survival.

AB - The interleukin-2 receptor alpha chain (IL-2Ra, CD25) plays a major part in shaping the dynamics of T cell populations following immune activation, due to its role in T cell proliferation and survival. Strategies to blunt the effector responses in transplantation have been developed by devising pharmaceutical agents to block the IL-2 pathways. However, such strategies could adversely affect the CD25+FOXP3+T regulatory (T reg) populations which also rely on intereukin-2 signaling for survival. The present study shows that a cohort of heart allograft recipients treated with Daclizumab (a humanized anti-CD25 antibody) display FOXP3 expression patterns consistent with functional T regulatory cell populations. High levels of FOXP3 were observed to correlate with lower incidence of and recovery from acute rejection, as well as lower levels of anti-donor HLA antibody production. Therefore, T reg populations appear fully functional in patients treated with Daclizumab, even when 5 doses were administered. By comparison, patients treated with fewer doses or no Daclizumab had a higher incidence of acute rejection, antibody production and graft failure. Therefore, our data indicates that Daclizumab treatment does not interfere with the generation of regulatory T cells and has a beneficial effect on heart allograft survival.

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KW - Rejection

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Anti-CD25 treatment and FOXP3-positive regulatory T cells in heart transplantation

Abstract

Keywords

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