Dendritic cell:CD4+ T cells interactions following injury.

Abstract

A number of laboratory and clinical studies have shown that extensive thermal injury induces a state of immune suppression, and that predisposes the injured host to critical morbidity and mortality. The principal outcome of such immune suppression is an increased susceptibility of injured host to opportunistic pathogens causing high risk of death. Both clinical and laboratory studies have shown that immune suppression with burns is characterized by monocyte/macrophage hyperactivity and/or depressed adaptive cell-mediated immunity associated with T lymphocyte functional deficit, viz., decreased IL-2 production and proliferation. Our studies showed that CD4+T cell apoptosis in burn or sepsis rats, although higher than in sham rats, was less than 50% of that in rats with the combined burn-plus-sepsis injury. Also, the CD4+ T cell responsiveness, assessed by IL-2 production and proliferation, in the burn or sepsis animals, though significantly less than in the sham group, was less than that in the burn-plus-sepsis group. The differences in the T cell deficits after the individual burn or sepsis injuries and the combined injury condition seemed well correlated with differences in mortality in these injured animal groups. From these observations, it seemed reasonable to hypothesize that T cell incompetence with burn or sepsis alone was mostly reversible which allowed for an eventual restoration of T cell homeostasis and competence compatible with high animal survival. On the other hand, the exacerbation of animal mortality with burn-plus-sepsis seemed related to a sustained loss of immune-competence and a critical deletion of antigen triggered T cells. (Supported by NIH MBRS SCORE Grant No. 3 S06 GM008043-34S1 project#6, and NSF MRI DBI-0520869)