Blocking CD40 – CD154 and CD80/CD86 – CD28 interactions during primary allogeneic stimulation results in T cell anergy and high IL-10 production
✍ Scribed by Stefaan W. Van Gool; Jan Vermeiren; Khadija Rafiq; Katrien Lorré; Mark de Boer; Jan L. Ceuppens
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 139 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
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-+ 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.