Cd3 haploinsufficiencies reveal the existence of differential CD3 chain functions in murine T cell development, phenotype and function.

摘要

CD3 chains are quite homologous but their specific roles in mature T cells are still unresolved. This cannot be studied in Cd3 KOs because they have no or few peripheral αβ T cells. We thus analysed the effect of haploinsufficiency in Cd3G (^e>), Cd3D (^e>) or Cd3E (^e>) in mouse T cell development, phenotype and function. Cd3 transcripts in haploinsufficient mice were uniformly 50% relative to normal mice, whereas CD3 proteins were around 70% of wild type levels, indicating excess biosynthesis. Survival to polymicrobial infection (a T-cell-dependent feature) showed differential effects among the three CD3 chains, with ^t>+/- and ^t>+/^t>, but not ^t>+/^t>, showing reduced survival. This did not correlate with surface TCR expression, as ^t>+/^t> and ^t>+/^t>, but not ^t>+/^t>, peripheral T cells showed a consistent reduction in surface TCRαβ expression (30-50% of wild type controls). Such reductions in TCR expression correlate with defects in late functional parameters such as IL-2 induction. We conclude that CD3 chains show differential but contrasting effects in vitro and in vivo.