Effector/memory CD8 + T cells synergize with co-stimulation competent macrophages to trigger autoimmune peripheral neuropathy

CD8+ T cell subpopulations and pro‐inflammatory cytokines in neuromyelitis optica spectrum disorder

“…Despite the previously reported pivotal role of CD4 + T cells in the pathogenesis of NMOSD and MS, accumulating data based on animals’ models and humans have initially explored the roles of CD8 + T cells involved in autoimmune disease 26‐28 . A study from the GBS suggested that peripheral myelin Ag specific CD8 + T cells exhibited an effector/memory phenotype and produced many pro‐inflammatory cytokines such as IFNγ and TNFα, which were required for the disease initiation in human and mice 16 . Meanwhile, research on experimental autoimmune encephalomyelitis (EAE) models further revealed that both CD4 + and CD8 + T cells recognized myelin oligodendrocyte glycoprotein (MOG) and contributed to trigger disease in vivo , even the disease was primarily driven by CD4 + T cells 26 .…”

“…Peripheral blood samples were collected from participants and prepared to be single cell suspensions as mentioned previously 16 . In brief, after washing with Alsevier’s solution (Gibco™), samples were lysed in ACK buffer (Thermo Fisher Scientific) at room temperature for 5 min.…”

“…Current pathogenic concepts implicate high frequency of CD8 + T E/M cells as the consequence of viral induced “memory inflation,” which are associated with autoimmune response in nervous system 16,18 . This distinct phenomenon is confirmed by eliminated expression of CD62L and acquired high expression level of CD45RO in CD8 + T cells from animal models and human patients, respectively 16,18,19 . After acute infection, effector CD8 + T cells generated into T SLEC cells (CD127 lo KLRG1 hi ) and T MP cells (CD127 hi KLRG1 lo ) capable of generating long‐lived memory CD8 + T cells to against infection 20 .…”

“…Although CD4 + T cells have been the main focus of NMOSD research for decades, 13,14 as one of the key players involved in neuroinflammation, CD8 + T cells were found to participate the immune cascades in development of NMOSD 15 . Accumulating data from peripheral neuropathic diseases indicated that CD8 + T cells played pivotal roles in triggering Guillain–Barre Syndrome (GBS), which is the prototypical autoimmune peripheral neuropathy 16 . Furthermore, as one of the most well studied autoimmune demyelinating diseases of CNS, MS was found to be correlated with abnormally increased frequencies and exaggerated pro‐inflammatory responses of CD8 + T cell subsets as well 17 .…”

“…Functionally, those CD8 + T cells are strong secretors of pro‐inflammatory cytokines of IFNγ and TNFα 21 . We previously reported a transgenic murine model with predisposed immune background, where CD8 + T cells have been primed and possess typical effector/memory phenotypes 16 . This model exhibits large amount of circulating CD44 hi CD62L lo and CD127 lo KLRG1 hi CD8 + T cells, which initiate spontaneous autoimmune peripheral neuropathy via secreting high levels of IFNγ and TNFα.…”