CD40 Expression by Microglial Cells Is Required for Their Completion of a Two-Step Activation Process during Central Nervous System Autoimmune Inflammation

摘要: Microglial cells are monocytic lineage that reside in the CNS and have capacity to become activated during various pathological conditions. Although it was demonstrated activation of microglial could be achieved vitro by engagement CD40-CD40L interactions combination with proinflammatory cytokines, exact factors mediate vivo autoimmunity ill-defined. To investigate role CD40 cell experimental autoimmune encephalomyelitis (EAE), we used bone marrow chimera mice allowed us distinguish from peripheral macrophages render deficient CD40. We found first step CD40-independent occurred EAE onset. The consisted proliferation up-regulation markers MHC class II, CD40, CD86. At peak disease, underwent a second activation, which characterized further enhancement marker expression along reduction proliferation. CD40-dependent failure CD40-deficient achieve full level correlated reduced expansion encephalitogenic T leukocyte infiltration CNS, amelioration clinical symptoms. Thus, our findings demonstrate on is necessary complete their process EAE, important for disease progression.