CD25 appears non essential for human peripheral T(reg) maintenance in vivo.
BACKGROUND
IL-2 has been reported to be critical for peripheral T(reg) survival in mouse models. Here, we examined T(reg) maintenance in a series of paediatric liver transplant recipients who received basiliximab, a therapeutic anti-CD25 monoclonal antibody.


RESULTS
FoxP3+ CD4 T cells were analyzed by flow cytometry before liver grafting and more than 9 months later. We found that in vivo CD25 blockade did not lead to T(reg) depletion: the proportion of FoxP3+ cells among CD4 T cells and the level of FoxP3 expression were both unchanged. IL-2Rbeta expression was enhanced in FoxP3+ cells both before and after basiliximab treatment, while the level of IL-2Rgamma expression was similar in T(regs) and non-T(regs). No significant change in the weak or absent expression of IL-7Ralpha and IL-15Ralpha expression on FoxP3+ cells was observed. Although the proportion of FoxP3+ cells among CD4 T cells did not vary, food allergies occurred more rapidly after liver grafting in patients who received basiliximab, raising questions as to T(reg) functionality in vivo in the absence of functional CD25.


CONCLUSIONS
CD25 appears non essential for human T(reg) peripheral maintenance in vivo. However, our results raise questions as to T(reg) functionality after therapeutic CD25 targeting.
de Goër de Herve
Marie-Ghislaine
MG
Unité d'Immunologie Biologique, CHU Bicêtre, Le Kremlin-Bicêtre, France.
Gonzales
Emmanuel
E
Hendel-Chavez
Houria
H
Décline
Jean-Luc
JL
Mourier
Olivia
O
Abbed
Karim
K
Jacquemin
Emmanuel
E
Taoufik
Yassine
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000077552:Basiliximab; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D005512:Food Hypersensitivity / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D053720:Interleukin-15 Receptor alpha Subunit / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
D000911:Antibodies, Monoclonal; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D053720:Interleukin-15 Receptor alpha Subunit; D053645:Interleukin-2 Receptor alpha Subunit; D053646:Interleukin-2 Receptor beta Subunit; D020395:Receptors, Interleukin-7; D011993:Recombinant Fusion Proteins; C415350:interleukin-7 receptor, alpha chain; D000077552:Basiliximab