Severe injury triggers antigen-specific T-helper cell dysfunction

Although it is established that post-injury immune dysfunction involves alt erations in T-cell function, the effects of injury on T-cell function in vi vo are poorly understood. This study uses a mouse injury model and an antig en immunization approach to investigate the influence of injury on antigen- specific T-helper cell function. We report here that injury triggered a sig nificant reduction in antigen-specific T-helper-1 (Th1)-dependent IgG2a ant ibody formation, while IgM, IgG1, and IgE production was unchanged. In addi tion, injury caused a reduction in cytokine production (IL-2, IFN gamma and IL-10) by antigen-stimulated T-cells. We also demonstrate that interleukin 12 (IL-12), a cytokine that promotes Th1 cell differentiation, restored Ig G2a antibody formation and corrected the injury-induced reduction in antige n-stimulated cytokine production. Taken together, these findings indicate t hat severe injury induces a dramatic reduction in Th1 cell function in vivo and suggest that therapies designed to restore Th1 cell function may be be neficial to the injured host.