The role of reactive oxygen species in triggering proliferation and IL-2 secretion in T cells

This paper examines the hypothesis that reactive oxygen species (ROS) play an important role as second messengers in T cell activation. Activation of T cells with phorbol ester in combination with either calcium ionophore, or anti-CD3 antibody results in a large rapid flux of ROS activity. In contra st, co-stimulation with CD28 does not enhance ROS activity. The ROS signal was sensitive to ascorbic acid, desferrioxamine and dimethyl sulfoxide, sug gesting that the major active species being generated was the hydroxyl radi cal, probably by iron-catalyzed decomposition of hydrogen peroxide. The gen eration of ROS in T cells was regulated by an accessory population within t he peripheral blood. An anti-CD2 antibody induced a strong ROS flux, sugges ting that the CD2/LFA-3 interaction may be important in this regulation. T cell activation was inhibited by the same panel of anti-oxidants as ROS gen eration, but much higher concentrations were required for inhibition of pro liferation and IL-2 release than those required to block ROS generation. Th ese data imply that ROS are not obligate second messengers for initiation o f T cell activation. The results are compatible, however, with a role for a ctivation-dependent T cell ROS generation in modulating the overall T cell response via autocrine and paracrine signalling pathways. (C) 1998 Elsevier Science Inc.