Blocking B7 and CD40 co‐stimulatory molecules decreases antiviral T cell activity

Inhibition of co‐stimulatory signals for T cells by interrupting CD80/CD86–CD28 and CD40–CD154 interactions is a promising approach to prevent transplant rejection and to induce graft tolerance. However, this tolerizing treatment might affect T cell reactivity towards all the antigens to which the immune system is exposed during treatment. We addressed the question whether such inhibition of co‐stimulatory ligands on human antigen presenting cells (APC) would affect T cell reactivity against a virus. This was tested in an in vitro system with freshly isolated human monocytes transduced with adenovirus (ad) containing either murine interferon‐γ (mIFN‐γ) or green fluorescent protein (GFP) as marker transgene. T cells co‐cultured with transduced monocytes proliferated and produced cytokines. These ‘primed’ T cells had strong antiviral activity as they subsequently killed ad/GFP‐transduced monocytes and reduced mIFN‐γ accumulation in coculture with ad/mIFN‐transduced monocytes. However, if priming had occurred in the presence of blocking anti‐CD40/CD80/CD86 MoAbs, generation of this antiviral activity was completely prevented. Moreover, T cells primed in the absence of co‐stimulatory cells failed to proliferate upon restimulation with adenovirus‐transduced monocytes. The results confirm that co‐stimulatory signals from APC are required for efficient induction of antiviral T cell activity and point to a potential infectious risk of blocking co‐stimulatory signals.

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