In vitro T cell unresponsiveness following low-dose injection of anti-CD3 MoAb

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Abstract
Anti‐CD3 MoAb treatment is widely used as an immunosuppressive therapy. In the present study we examined the in vitro T cell response in mice having received 24 h before a single i.v. injection of 10 μg of anti‐CD3 MoAb. We found that splenocytes from these mice displayed a dramatically decreased proliferative response to the T cell mitogens concanavalin A (Con A), anti‐CD3, phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA) + calcium ionophore, while the effect of lipopolysaccharide (LPS) was not impaired. T cell suppression persisted for about 10 days after anti‐CD3 injection, returning to normal within 15 days. The F(ab')2 fragment of anti‐CD3 had no such effect, indicating the requirement for in vivo activation. At the dose used, anti‐CD3 resulted neither in T cell depletion nor in down‐modulation of the CD3 T cell receptor (TCR) complex. The low proliferation was also not explained by apoptosis, following secondary challenge with Con A. Splenocytes from anti‐CD3‐injected mice were highly responsive to IL‐2, but generated little or no IL‐2, IL‐3, IL‐4 and interferon‐gamma (IFN‐γ) when exposed to Con A. Normal cytokine production could not be restored by the addition of optimal doses of IL‐2 during Con A stimulation. Transforming growth factor‐beta (TGF‐β) was the only cytokine whose mRNA expression was not modified in stimulated splenocytes from anti‐CD3‐injected mice. Furthermore, anti‐TGF‐β antibodies increased Con A‐induced T cell proliferation, but not cytokine production.