The Effect Of Serious Trauma On The Capacity In Inducing T Cell Responses Of Bone Marrow Derived Dendritic Cells In Mice

Trauma is a leading threat to health of human being and productivity of human society. Trauma often leads to severe disorder of the immune system with an increased susceptibility to septic complications and MODS. A better understanding of these mechanisms would assist the introduction of preventive and therapeutic strategies into clinical practice.Dendritic cells (DC) are professional antigen presenting cells, which display an extraordinary capacity to stimulate naive T cells and initiate primary immune responses. Being a bridge between innate immunity and adaptive immunity, DCs play an important role of immunoregulation in some diseases such as infections, tumor, allograft reactions, allergic and autoimmune diseases, etc.Studies have shown significant changing in quantity, antigen-presentation and cytokine production of DC after trauma and following complications. But the effect of trauma on differentiation and function of bone marrow derived dendritic cells (BMDC) in mice has not been reported yet.Objectives:To observe the effect of serious trauma on the capacity in inducing allogeneic T cell responses of BMDC.Methods:1. Bone marrow was isolated 24 h after hemorrhage combined with closed femur fracture. BMDCs were induced in vitro by recombinant murine granulocyte/macrophage- colony stimulating factor (rmGM-CSF). 2. The capacity of immature DC and mature DC in inducing allogeneic T cells responses was determined by mixed lymphocyte reaction (MLR).3. The expressions of major histocompatibility complex class II (MHC II), costimulatory molecules such as CD40, CD80, and CD86 on DC surface were measured using flow cytometry.4. Interleukin-12 p40, IL-12 p70 and interleukin-10 levels in lipopolysaccharide (LPS)-stimulated DC supernatants were detected by enzyme-linked immunosorbent assay (ELISA) kits.Results:1. The percentage of BMDCs from traumatized mice has no obvious difference with normal controls under the equal condition(92.3±8.5% vs 91.8±6.9%,P >0.05). But total amount of BMDCs from traumatized mice was significantly lowered than that of normal controls.2. BMDCs from traumatized mice, regardless of LPS-induced maturation, mediated significant reduced MLR in comparison with normal controls (P <0.05).3. CD40 expression on BMDC from traumatized mice, before or after LPS stimulation, was significantly lowered than that of normal controls (4±1.0% vs 22±3.5%, P <0.01, 56±7.5% vs 91±8.0%, P <0.01), but no significant changes of MHC II, CD80 and CD86 expression on BMDCs were observed between the two groups.4. The levels of IL-12 p40, IL-12 p70 in LPS-stimulated BMDCs supernatants from traumatized mice were lower than those in normal controls (45±6.5 ng/L vs 78±6.8 ng/L, P <0.05, 9±1.0 ng/L vs 18±1.9 ng/L, P <0.05), while no significant difference of IL-10 levels was observed between the two groups.Conclusions:BMDCs from traumatized mice show reduced capacity in inducing T cells responses, which may be partially attributable to decreased expression of costimulatory molecule CD40 and unadequate IL-12 secretion.