Intercellular adhesion molecule-1 inhibits interleukin 4 production by naive T cells

The type of cytokines produced during T cell responses determines susceptib ility or resistance to many pathogens and influences the development of aut oimmunity and allergy, To define the role of individual accessory molecules in cytokine production during primary immune responses, Drosophila cell li nes expressing murine major histocompatibility complex class Il molecules w ith defined combinations of accessory molecules were used to present peptid e antigen to naive T cell receptor transgenic T cells. Significantly, expre ssion of B7.1 or B7.2 without additional accessory molecules led to very hi gh production of interleukin (IL)-4, which contrasted with minimal IL-4 pro duction elicited by conventional antigen presenting cells (APC), However, c oexpression of ICAM-1 and B7 on Drosophila APC induced little IL-4, suggest ing an inhibitory role for intercellular adhesion molecule-1 (ICAM-1). In s upport of this idea, stimulation of T cell receptor transgenic T cells with peptide presented by splenic APC devoid of ICAM-1 (from ICAM-1-deficient m ice) led to high IL-4 production. Thus, the level of IL-4 production by nai ve CD4(+) T cells during typical primary responses appears to be controlled , at least in part, by T-APC interactions involving ICAM-1.