The compartmentalized inflammatory response in the multiple sclerosis brain is composed of tissue-resident CD8+ T lymphocytes and B cells

Abstract

The nature of the inflammatory response in the MS brain is poorly defined. Machado-Santos et al. report that chronic inflammation is dominated by tissue resident CD8+ T-cells and CD20+ B-cells, which are activated in lesions with demyelinating or neurodegenerative activity.

Pathology of inflammatory diseases of the nervous system: Human disease versus animal models

“…However, convincing evidence that in these conditions cells of the adaptive immunity are activated through local antigen recognition, with subsequent proliferation and clonal expansion is largely absent. Thus, on a quantitative neuropathological basis the lymphocytic inflammatory reaction in such conditions is marginal in comparison to that seen in classical inflammatory diseases of the brain and spinal cord (Machado‐Santos et al, ). Conditions of neuroinflammation and the respective consequences will be discussed in detail in other chapters of this special issue.…”

“…Such T‐cell populations are mainly found experimentally in models of virus encephalitis, where such cells persist in the CNS as immune guardians after virus clearance and can be reactivated by re‐exposure to their cognate antigen (Schenkel & Masopust, ; Steinbach et al, ). Regarding B‐cells, CD19 and CD20 positive B‐cells dominate in active MS lesions and transform into immunoglobulin producing plasmablasts and plasma cells with lesion maturation (Frischer et al, ; Machado‐Santos et al, ). So far experimental models, defining the role of B‐cells in the induction and propagation of inflammation in the brain and spinal cord are missing.…”

“…However, these findings also raise the question, whether the commonly used model of CD4 + T‐cell dependent EAE is suitable to study the role of microglia and other tissue resident myeloid cells in relation to human inflammatory diseases of the CNS. As mentioned above, in most human inflammatory brain diseases inflammation is dominated by CD8 + T‐cells or, less frequently by B‐cells (Machado‐Santos et al, ). For such conditions, experimental models are rare at present and only sparse data on microglia and macrophages are available.…”

“…The vast majority of human acute and chronic inflammatory brain diseases, however, reflect an inflammatory reaction, massively dominated by MHC Class I restricted CD8 + T-lymphocytes (Machado-Santos et al, 2018). In some of these diseases, such as paraneoplastic encephalitis (Dauvilliers et al, 2013), Rasmussen's encephalitis (Bien et al, 2002), and viral encephalitis (Cox, Kahan, & Zajac, 2013;Laukoter et al, 2017), evidence for tissue injury and elimination of infected cells, which is directly mediated by cytotoxic CD8 + lymphocytes, has been provided.…”

“… Note : The table compares the key features of inflammatory lesions in the central nervous system mediated by different T‐cell populations, B‐cells, and innate immunity in rodent models and humans, also describing the reaction patterns of microglia/macrophages and astrocytes. References 1: Ajami et al (), 2: Ben‐Nun, Wekerle, and Cohen (), Lassmann et al (), 4: Wolf et al (), 5: Blaabjerg et al (). 6: Mayo et al (), 7: Basso et al (). 8: Bradl and Lassmann (), 9: Linington, Bradl, Lassmann, Brunner, and Vass (), 10: Misu et al (), 11: Pohl et al, , 12: Storch et al (). 13: Bien et al (), 14: Cabarrocas, Bauer, Piaggio, Liblau, and Lassmann (), 15: Dauvilliers et al (), 16: Ji, Perchellet, and Goverman (), 17: Laukoter et al (), 18: Na et al (), 19: Saxena et al (), 20: Steinbach et al (), 21: Tröscher et al (). 22: Machado‐Santos et al (), 23: van Nierop et al (), 24: Zrzavy et al (). 25: Felts et al (), 26: Marik, Felts, Bauer, Lassmann, and Smith (), 27: Nau and Brück (2002). …”