Anti-CD25 treatment and FOXP3-positive regulatory T cells in heart transplantation.
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.
Vlad
G
G
The Department of Pathology, Columbia University, New York, NY 10032, United States.
Ho
E K
EK
Vasilescu
E R
ER
Fan
J
J
Liu
Z
Z
Cai
J W
JW
Jin
Z
Z
Burke
E
E
Deng
M
M
Cadeiras
M
M
Cortesini
R
R
Itescu
S
S
Marboe
C
C
Mancini
D
D
Suciu-Foca
N
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006680:HLA Antigens / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006680:HLA Antigens; D053645:Interleukin-2 Receptor alpha Subunit