IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor alpha subunit CD25.
IL-2 is crucial to T cell homeostasis, especially of CD4(+) T regulatory cells and memory CD8(+) cells, as evidenced by vigorous proliferation of these cells in vivo following injections of superagonist IL-2/anti-IL-2 antibody complexes. The mechanism of IL-2/anti-IL-2 antibody complexes is unknown owing to a lack of understanding of IL-2 homeostasis. We show that IL-2 receptor alpha (CD25) plays a crucial role in IL-2 homeostasis. Thus, prolongation of IL-2 half-life and blocking of CD25 using antibodies or CD25-deficient mice led in combination, but not alone, to vigorous IL-2-mediated T cell proliferation, similar to IL-2/anti-IL-2 antibody complexes. These data suggest an unpredicted role for CD25 in IL-2 homeostasis.
Division of Immunology and Allergy, University Hospital of Lausanne, CH-1011 Lausanne, Switzerland.
Sven
S
Létourneau
Ester M M
EM
van Leeuwen
Carsten
C
Krieg
Chris
C
Martin
Giuseppe
G
Pantaleo
Jonathan
J
Sprent
Charles D
CD
Surh
Onur
O
Boyman
D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D006207:Half-Life; D006706:Homeostasis; D007074:Immunoglobulin G / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011961:Receptors, Fc / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism
D019138:Antibodies, Blocking; D000936:Antigen-Antibody Complex; C508018:Il2ra protein, mouse; D007074:Immunoglobulin G; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins