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Title: Blocking CD40 - CD154 and CD80/CD86 - CD28 interactions during primary allogeneic stimulation results in T cell anergy and high IL-10 production
Authors: Van Gool, Stefaan ×
Vermeiren, Jan
Rafiq, K
Lorr, K
de Boer, M
Ceuppens, Jan #
Issue Date: 21-Sep-1999
Publisher: Williams & Wilkins
Series Title: European Journal of Immunology vol:29 issue:8 pages:2367-75
Abstract: Although CD28 triggering provides an important co-stimulatory signal to T cells, blocking the CD80/CD86 - CD28 interaction with CTLA-4lg fusion protein is not sufficient for tolerance induction in vivo or in vitro. According to more recent data, interruption of the CD40 - CD154 interaction might complement the effect of CTLA-4lg and induce graft acceptance. We studied the effects of a blocking anti-CD40 monoclonal antibody (mAb) and/or blocking anti-CD80/anti-CD86 mAb in cultures of human peripheral blood mononuclear cells (PBMC) stimulated with allogeneic PBMC. T cells activated by alloantigens in the presence of anti-CD80, anti-CD86 and anti-CD40 entered a state of alloantigen-specific non-responsiveness as evidenced upon restimulation by lack of proliferation, cytotoxic activity, and IL-2, IL-5 and IL-13 production. IFN-gamma production during restimulation was less than in the control cultures, while the production of IL-10 was enhanced. Addition of recombinant IL-2 during the restimulation rescued alloantigen-specific activity. We conclude that the simultaneous blocking of the CD40 - CD154 and CD80/CD86 - CD28 interaction during allogeneic T cell activation induces T cell anergy. Since anergic cells induced by this treatment still produce high levels of IL-10, the latter could contribute to modulation of antigen-presenting cell activity and to bystander suppression of residual reactive T cells.
ISSN: 0014-2980
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Clinical Immunology
Section Child - Miscellaneous (-)
Pediatric Hematology & Oncology Section (-)
Laboratory of Pediatric Immunology
× corresponding author
# (joint) last author

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