In the past we and other investigators have attributed the post-injury systemic inflammatory response syndrome (SIRS) to hyperactivity of the innate immune system and the subsequent compensatory anti- inflammatory response syndrome (CARS) to dysfunction of the adaptive immune system. However, more recent evidence supports the following testable hypothesis upon which the present proposal is based: Injury initially activates the adaptive immune system through endogenous antigen stimulation, as well as the innate immune system, resulting in SIRS which is followed by a compensatory down-regulation, CARS, characterized by an inhibitory T cell phenotype and decreased ability of the innate immune system to resist infection. We will use both human and animal studies to test this hypothesis with the following specific aims: 1. Delineate the participation of T cells in the early inflammatory (SIRS) response to injury and the relationship of this activity to subsequent CARS. 2. Determine the molecular mechanisms involved in the participation of T cells in the SIRS and CARS responses after injury. 3. Define the interactions of cells of the innate and adaptive immune systems in the induction of the SIRS and CARS responses to injury in genetically altered mice.
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| O'Leary, Fionnuala M; Tajima, Goro; Delisle, Adam J et al. (2011) Injury-induced GR-1+ macrophage expansion and activation occurs independently of CD4 T-cell influence. Shock 36:162-9 |
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