gms | German Medical Science

Objectives: Major injury causes a state of immunosuppression that increases the susceptibility to opportunistic infections leading to an increased morbidity of those patients. Our previous work demonstrated that, after soft tissue trauma, antigen-specific T cell responses are impaired through a so far unknown mechanism involving T cells and mature natural killer (NK) cells. Upon exposure to innate cytokines T cells are activated independent of their cognate antigen (“bystander” activation) and may acquire regulatory activity. NK cells support the immune defense against invading bacteria through secretion of IFN-g. We investigated whether bystander activation of T cells takes place after skeletal muscle injury and whether it is linked to NK cells.

Methods: A blunt skeletal muscle injury was induced in mice and leukocytes of the draining lymph nodes were isolated. The expression of CD69, as a representative marker for early activation, on diverse CD8+ T cell subpopulations (naÏve, effector/effector memory, and central memory T cells) was determined 24, 48, and 96 hours after injury. NK cells were analyzed in terms of their maturation status and the expression of IFN-g in response to Staphylococcus aureus. The expression of mRNA of cytokines that are known to mediate bystander activation of T cells (IL-12p40, IL-2, IL-18, IL-15 and type I interferon) was analyzed 3, 6, and 16 hours after injury using real-time PCR.

Results and conclusion: A higher expression of IL-12p40 mRNA and type I interferon was found in the popliteal lymph node 3 and 6 hours after traumatic skeletal muscle injury, respectively. However, the expression of IL-2, IL-15, or IL-18 mRNA did not differ after trauma. The percentage of CD69 expression increased on naive and central memory CD8+ T cells within 24 hours after injury. Moreover, the percentage of CD69+ virtual memory T cells that possess regulatory activity increased after 24 hours. This activation of virtual memory T cells could also be seen 48 hours after injury. NK cells displayed a higher maturation state after trauma and increased in number one and two days after trauma. NK cells produced less IFN-g after trauma. Preliminary data show that prior depletion of CD8+ T cells in vivo prevented the maturation of NK cells after trauma and restored the IFN-g synthesis.

Skeletal muscle injury induces the expression of IL-12 and type I interferon in the draining popliteal lymph node that might mediate an antigen-independent activation of CD8+ T cells. The protracted activation of virtual memory T cells might indicate a special role of these T cells within the regulation of immune response after skeletal muscle injury. NK cells mature and are alleviated in IFN-g production after trauma presumably through interaction with CD8+ T cells. The reduced activity of NK cells might contribute to the disturbed immune defense against bacterial infections after trauma.