Induction of global anergy rather than inhibitory Th2 lymphokines mediatesposttrauma T cell immunodepression

Depressed mitogen-induced IL-2 and IFN-gamma responses after severe mechani cal or thermal injury are postulated to result from an expansion of Th2 lym phocytes with concomitant excessive production of IL-4 and/or IL-10. Here, we simultaneously assessed proliferation and Th1 (IFN-gamma) versus Th2 (IL -10, IL-4) lymphokine production in trauma patients' isolated T cells stimu lated in a costimulation sufficient, antigen presenting cell independent sy stem (anti CD3 + anti-CD4). T cells with depressed proliferation and IL-2 p roduction simultaneously lost IL-4, IL-10, and IFN-gamma protein and mRNA r esponses. Exogenous IL-12 addition did not restore IFN gamma responses, but exogenous IL-2 partially restored IL-4, IFN-gamma, and IL-10 production. A lthough initially partially restored by exogenous IL-2 or stimulation with PMA + ionomycin, patient T cells with persisting anergy progressively lost even these lymphokine and proliferative responses. Development of global T cell anergy was not a result of lost T cell viability or protein synthesis, since it corresponded to predominance of anergic T cells with upregulated expression of CD11b, but downregulated CD28 and CD3 expression. Thus, the s ubset of posttrauma patients whose isolated T cells become unresponsive exp erienced progressively worsening global anergy, mediated not by an increase d production of Th2 lymphokines, but possibly by T cell incapacity to be ac tivated through TCR triggering or Ca2+ mobilization. (C) 2000 Academic Pres s.