Effects of anti-IL-4 receptor monoclonal antibody on in vitro T cell cytokine levels: IL-4 production by T cells from non-atopic donors.

IL-4 is a pleiotropic cytokine which is involved in the development of atopic diseases. Only limited data exist on IL-4 production in humans, and the relative contribution to atopy of either unbalanced IL-4 production, or increased IL-4-responsiveness of target cells, is still unknown. The use of a MoAb to the IL-4 receptor alpha-chain (IL-4Ralpha) enabled us to demonstrate that IL-4 production in vitro is usually underestimated, due to in vitro consumption, even in cultures of purified T cells. When IL-4 consumption was blocked, it became evident that CD80 and CD86 both provide effective costimulatory signals for high IL-4 production. Moreover, we found that even stimulation with a soluble antigen (tetanus toxoid) induces IL-4 production by T cells from healthy non-atopic donors. Both sets of data imply that IL-4 is not required for IL-4 production by memory and/or effector T cells. Our data further show that endogenous IL-4 activity modulates IL-10 and interferon-gamma production by T cells in opposite directions. The use of this receptor-blocking antibody will thus be helpful for in vitro studies on IL-4 regulation. Consumption of IL-4 by different cell types during in vitro cultures might have interfered with previous attempts to quantify IL-4 production by human T cells.