PMC:4136538 / 26434-27953 JSONTXT

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CD40 is a cell surface receptor expressed by activated microglia [27–30]. CD40 ligand (CD154) is a surface protein primarily expressed by activated CD4+ T lymphocytes [21]. Although it is known that the CD154-CD40 interaction between Th1 cells and macrophages promotes macrophage responses [21] and that the interaction between microglial CD40 and CNS infiltrating-T lymphocyte CD154 has been linked to the pathogenesis of various CNS diseases [14–19], our data indicate that it is unlikely that lumbar spinal cord-infiltrating CD4+ T lymphocytes mediate their pro-nociceptive effects through CD154-mediated interactions with spinal cord microglial CD40. Similar to our observation, it has been reported that CD40, but not CD154, was required for mounting an optimal response against M tuberculosis infection, and this discrepancy was attributed to an interaction between CD40 and a non-CD154 CD40 ligand [31]. The discrepancy in the development of behavioral hypersensitivity between CD40 KO and CD154 KO mice suggest that such an alternative CD40 ligand may be involved in CD40-mediated pro-nociceptive effects. In addition, we previously did observe a reduction in the L5Tx-induced increase of microglia in the lumbar spinal cord in CD4 KO mice [32]. Thus, further studies are necessary to explore other factors involved in the interaction between CD4+ Th1 lymphocytes and microglia."}