Anergy of antigen-specific T lymphocytes is a potent mechanism of intravenously induced tolerance.
Intravenous (i.v.) injection of an antigen before immunization has been shown to be a potent way to induce suppression at the T-cell level. In this study we demonstrate an almost complete suppression of arthritis (using antigen-induced arthritis as a model) by i.v. injection of 100 micrograms hen egg lysozyme (HEL) 7 days before immunization. Underlying mechanisms, including suppression by CD8+ T lymphocytes, suppression by T-helper 2 (Th2) or anergy of antigen-specific T lymphocytes, were studied. In vivo treatment with either anti-CD8 or anti-interleukin-4 (IL-4) could not abrogate i.v.-induced tolerance. Lymphocyte stimulation assays showed reduced antigen-specific proliferative responses and IL-2 production in tolerized mice. The possible role of soluble suppressive cytokines was examined in vitro by adding anti-IL-4, anti-IL-10 or anti-transforming growth factor-beta (TGF-beta). Neutralization of these factors could not diminish suppression. Finally, anergy of antigen-specific T lymphocytes was tested as a possible mechanism for i.v.-induced tolerance. Results demonstrated that reduced proliferative T-cell responses were reversible: incubation of tolerized lymph node cells for 5 days in added recombinant (r)IL-2 fully restored proliferative capacity back to normal. We therefore conclude that the main mechanism of i.v.-induced tolerance in our model is anergy of antigen-specific T lymphocytes.
Jacobs
M J
MJ
Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
van den Hoek
A E
AE
van de Putte
L B
LB
van den Berg
W B
WB
D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D001168:Arthritis / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D017635:Clonal Anergy / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D007275:Injections, Intravenous; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000008:administration & dosage / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D000939:Epitopes; D007376:Interleukin-2; D015847:Interleukin-4; D009113:Muramidase