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Abstract
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 posttrauma
is not innately deleterious or immediately responsible for anergy, but may predispose
to later development of T cell anergy, possibly due to a more stringent requirement
for activation of the remaining naive T cells.
Methods. A total of 30 blunt trauma and burn patients were assessed twice weekly for the following
parameters: (1) clinical outcome expressed as severity of organ dysfunction as measured
by the multiple organ dysfunction syndrome score, (2) proliferative response of highly
purified T cells to anti-CD3/anti-CD4, (3) level of apoptosis as determined by flow
cytometric analysis of propidium iodide-stained monocyte reduced peripheral blood
mononuclear cells, either unstimulated or in response to mitogenic challenge or Fas
(CD95) 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 maximum anergy (lowest proliferative response)
correlates to diminished apoptotic response. Increased T cell apoptosis can be stimulated
by anti-Fas antibody 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 who later develop
T cell anergy have increased T cell apoptosis earlier in their 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 cell depletion occurring before complete activation
and expansion of the posttrauma T cell response may presage anergy and subsequent
organ failure.
Keywords
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© 2000 Academic Press. Published by Elsevier Inc. All rights reserved.
