PMC:4136538 / 4936-6755
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4136538","sourcedb":"PMC","sourceid":"4136538","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4136538","text":"Further, the underlying mechanism through which selected infiltrating helper T cell subtypes contribute to peripheral nerve injury-induced sensory hypersensitivity is still unclear. It has been proposed that infiltrating T lymphocytes interact with central nervous system (CNS) resident glial cells, including both astrocytes and microglia, to promote CNS pro-inflammatory responses that further contribute to central sensitization and persistent pain behaviors [3,12]. It is well-known that Th1 cells further activate macrophages through several co-stimulatory pathways. Previously, we have reported that microglial CD40 plays a critical role in the development of L5Tx-induced mechanical hypersensitivity [13]. As the ligation between CD40 expressed by macrophages and CD40 ligand (CD154) expressed by Th1 cells plays a key role in enhancing macrophage function in the peripheral immune system and microglia are the monocyte/macrophage lineage cells in the CNS, it is possible that infiltrating T lymphocytes play their pro-nociceptive role by interacting with microglia through the CD40–CD154 pathway. In fact, this very interaction has been linked to the pathogenesis of various CNS diseases, including multiple sclerosis and Alzheimer’s disease [14–19]. Thus, in this current study, we investigated whether CD154+CD4+ T lymphocytes contribute to the maintenance of long-term behavioral hypersensitivity with CD154 knockout (KO) mice. In addition, to examine whether lumbar spinal cord-infiltrating CD4+ T lymphocytes contribute to the maintenance of L5Tx-induced mechanical hypersensitivity through the regulation of spinal cord astrocytic activity, we also examined lumbar spinal cord astrocytic glial fibillary acidic protein (GFAP) immunoreactivity in time course studies in both wild type (WT) and CD4 KO 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