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- Title
Anergy of antigen-specific T lymphocytes is a potent mechanism of intravenously induced tolerance.
- Authors
Jacobs, M. J. M.; van den Hoek, A. E. M.; van de Putte, L. B. A.; van den Berg, W. B.
- Abstract
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 iv. injection of 100 μg hen egg lysozyme (HEL) 7 days before immunization. Underlying mechanisms, including suppression by CDS + 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-β (TGF-β). 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 I lymphocytes.
- Subjects
ANTIGENS; LYMPHOCYTES; INTRAVENOUS injections; T cells; IMMUNIZATION; BIOCOMPATIBILITY
- Publication
Immunology, 1994, Vol 82, Issue 2, p294
- ISSN
0019-2805
- Publication type
Article