DELAYED IGG2 HUMORAL RESPONSE IN INFANTS IS NOT DUE TO INTRINSIC T-CELL OR B-CELL DEFECTS

The physiologically low or absent IgG2 responses of infants have been attributed to T or a cell functional immaturity. We have analyzed the capacity of adult and neonatal T lymphocytes to secrete IgG2 switch fa ctor (IgG2-SF) and the capacity of neonatal a cells to respond to such factors, The IgG2-SF capacity was assessed on CD40-activated naive a cells, measuring IgG2 by ELISA in supernatants of cultures performed i n the presence of IL-10, T cells secreted IgG2-SF together with IL-2 a nd IFN-gamma, after activation with a combination of anti-CDP, anti-CD 28 and phorbol myristate acetate (T(h)1-like activation), In contrast, activation with anti-CD3 and anti-CD28, which yielded IL-4 and IL-10 but neither IL-2 nor IFN-gamma (T(h)2-like activation), did not result in the secretion of IgG2-SF. The supernatant of activated neonatal T cells contained IgG2-SF, Neonates' a cells produced almost as much IgG 2 as did naive adult a cells. The effect of IgG2-SF was further demons trated by its ability to induce 3-15% of CD40-activated naive a cells to express cytoplasmic IgG2 regardless of the presence of IL-10, This study demonstrates that: (i) IgG2 switch can be T cell dependent in hu mans, (ii) IgG2-SF is produced with T(h)1-like cytokines and (iii) low IgG2 responses in infants do not result from either an inability of T cells to produce IgG2-SF or an inability of a cells to undergo IgG2 s witch in vitro.