In vitro T cell unresponsiveness following low-dose injection of anti-CD3 MoAb |
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| Authors: | A. BEN-AMOR M. C. LEITE-DE-MORAES F. LEPAULT E. SCHNEIDER F. MACHAVOINE A. ARNOULD L. CHATENOUD M. DY |
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| Affiliation: | Université René Descartes-Paris V, CNRS URA 1461, Paris, France;*INSERM U25, Hôpital Necker, Paris, France |
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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. |
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| Keywords: | anti-CD3 MoAb cytokines IL-2 transforming growth factor-beta 1 T cell unresponsiveness |
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