Relationships between T lymphocyte apoptosis and anergy following trauma

Background. Severely injured trauma patients experience T cell depletion. A subset of these patients also develop T cell unresponsiveness (anergy), as characterized by the failure of their T cells to proliferate or to produce T lymphokines in response to a direct stimulus through the T cell receptor . We hypothesized that T cell apoptosis plays a role in the development of posttrauma T cell depletion and/or T cell anergy by deleting an activated T cell population, We found that moderately increased T cell depletion postt rauma is not innately deleterious or immediately responsible for anergy, bu t may predispose to later development of T cell anergy, possibly due to a m ore stringent requirement for activation of the remaining naive T cells. Methods. A total of 30 blunt trauma and burn patients were assessed twice w eekly for the following parameters: (1) clinical outcome expressed as sever ity of organ dysfunction as measured by the multiple organ dysfunction synd rome score, (2) proliferative response of highly purified T cells to anti-C D3/anti-CD4, (3) level of apoptosis as determined by how cytometric analysi s of propidium iodide-stained monocyte reduced peripheral blood mononuclear cells, either unstimulated or in response to mitogenic challenge or Fas (C D95) stimulation. Results. A wide range of apoptosis levels are seen in the patients' T cells . Apoptosis is increased when all trauma patients' T cells are compared to T cells of normal volunteers. However, at the time a patients' T cells are anergic, there is no increased level of apoptosis, In fact, the point of ma ximum anergy (lowest proliferative response) correlates to diminished apopt otic response. Increased T cell apoptosis can be stimulated by anti-Fas ant ibody in trauma patients' responsive T cells but not in maximally anergic T cells. These data suggest that patients' T cell anergy is not an immediate result of apoptotic T cell depletion upon stimulation. However, patients w ho later develop T cell anergy have increased T cell apoptosis earlier in t heir clinical course than patients who never experience T cell anergy, Conclusions. Increased levels of apoptosis are not directly associated with negative trauma patient outcome nor the immediate cause of T cell anergy. However, unusually high levels of apoptosis and development of severe T cel l depletion occurring before complete activation and expansion of the postt rauma T cell response may presage anergy and subsequent organ failure, (C) 2000 Academic Press.