Polyethylene glycol-modified IL-2 abrogates superantigen-induced anergy without affecting peripheral clonal deletion in vivo.
As compared with the native molecule, recombinant human interleukin-2 that is modified by covalently attached polyethylene glycol residues (IL-2-PEG) exhibits a markedly enhanced half-life in vivo, thus facilitating its biological evaluation. We have characterized the effect of IL-2-PEG on the Staphylococcus aureus enterotoxin B (SEB)-induced tolerance of peripheral SEB-reactive (V beta 8+) T cells. Treatment with sublethal doses of IL-2-PEG does not modulate (inhibit or enhance) the SEB-triggered apoptosis and deletion of V beta 8+ T cells. In contrast, in vivo treatment with IL-2-PEG partially abolishes the SEB-triggered anergy of V beta 8+ T cells, i.e., the failure to proliferate in response to SEB in vitro. To abolish SEB-triggered anergy, IL-2-PEG must act for an extended period in vivo; short term treatment in vivo (2 days) or exposure of anergic T cells to IL-2 in vitro fails to reconstitute proliferative responses. Moreover, the effect of in vivo treatment with IL-2-PEG on lymphokine production by anergic T cells is partial. IL-2-PEG restores IL-4-dependent autocrine proliferation in response to SEB but does not reestablish defective IL-2 production. These data are compatible with the notion that IL-2 is a regulator of postdeletional rather than deletional T cell tolerance.
González-García
A
A
Centro Nacional de Biotecnología (CSIC), Universidad Autónoma de Madrid, Spain.
Marchetti
P
P
Castedo
M
M
Zamzami
N
N
Tarazona
R
R
Martínez-A
C
C
Kroemer
G
G
D000818:Animals; D017635:Clonal Anergy / Q000187:drug effects*; D017637:Clonal Deletion / Q000187:drug effects*; D004768:Enterotoxins / Q000276:immunology*; D006207:Half-Life; D007376:Interleukin-2 / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D004768:Enterotoxins; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C067245:interleukin-2, polyethylene glycol-modified; C031818:enterotoxin B, staphylococcal; D011092:Polyethylene Glycols