Lymphocyte targeting of the brain in adoptive transfer cryolesion-EAE

Lake, Jonathan I.; Weller, Roy O.; Phillips, Marian J.; Needham, Michelle

doi:10.1002/(sici)1096-9896(199901)187:2<259::aid-path212>3.0.co;2-h

Cited by 55 publications

(19 citation statements)

References 29 publications

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“…The significance of cervical LN in the development of EAE is demonstrated by the finding that complete removal of the cervical LN markedly reduced the severity of cryolesion-enhanced EAE in Lewis rats (61). Moreover, there are indications that encephalitogenic T cells primed in the cervical LN may preferentially target the brain (62). The results of our study support the importance of the cervical LN in EAE in the modulation of autoreactivity.…”

Section: Discussionmentioning

confidence: 99%

Transfer of Central Nervous System Autoantigens and Presentation in Secondary Lymphoid Organs

Vos¹,

Meurs²,

Brok

et al. 2002

The Journal of Immunology

250

181

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Dendritic cells are thought to regulate tolerance induction vs immunization by transferring Ags and peripheral signals to draining lymph nodes (LN). However, whether myelin Ag transfer and presentation in LN occurs during demyelinating brain disease is unknown. In this study, we demonstrate redistribution of autoantigens from brain lesions to cervical LN in monkey experimental autoimmune encephalomyelitis (EAE) and in multiple sclerosis (MS). Immunohistochemical analysis revealed significantly more cells containing myelin Ags in cervical LN of monkeys with EAE compared with those of healthy control monkeys. Myelin Ags were observed in cells expressing dendritic cell/macrophage-specific markers, MHC class II, and costimulatory molecules. Moreover, these cells were directly juxtaposed to T cells, suggesting that cognate interactions between myelin-containing APC and T cells are taking place in brain-draining LN. Indeed, myelin Ag-reactive T cells were observed in cervical LN from marmosets and rhesus monkeys. Importantly, these findings were paralleled by our findings in human tissue. We observed significantly more myelin Ag-containing cells in LN of individuals with MS compared with those of control individuals. These cells expressed APC markers, as observed in marmosets and rhesus monkeys. These findings suggest that during MS and EAE, modulation of T cell reactivity against brain-derived Ags also takes place in cervical LN and not necessarily inside the brain. A major implication is that novel therapeutic strategies may be targeted to peripheral events, thereby circumventing the blood-brain barrier.

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Section: Discussionmentioning

confidence: 99%

Transfer of Central Nervous System Autoantigens and Presentation in Secondary Lymphoid Organs

Vos¹,

Meurs²,

Brok

et al. 2002

The Journal of Immunology

250

181

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“…148 Such activated T cells migrate to cervical LN, interact with antigens drained from the CNS and drive autoimmunity. 62,149,150 Consequently, perivascular CNS lymphatics might balance solute exchange and regulate critical brain parenchymal neuroimmunological reactions, and manipulation of neurolymphatics is under study as a therapeutic approach. 62 …”

Section: Role Of the Lymphatic System In Cns Diseasementioning

confidence: 93%

Anatomy and roles of lymphatics in inflammatory diseases

Al‐Kofahi

Yun

Minagar

et al. 2017

Clinical & Exp Neuroim

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The lymphatic system maintains tissue homeostasis by transporting interstitial fluid, lipids and debris from tissues to the main circulation, and delivers antigen and antigen presenting cells to local lymph nodes where they elicit immune responses. During inflammation, lymph flow increases to limit edema and prevents tissue antigen-presenting cell transport. Lymphatics also adjust their contractile activity to increase fluid transfer during acute inflammation. Conversely, chronic inflammation can provoke lymphostasis, which might limit pathogen spread within the circulation; however, decreased lymph flow leads to the persistence of immune cells and mediators in tissues to intensifying injury. Here, we review lymphatic structure function within the gut, heart and central nervous system, discussing potential roles of these lymphatics in the etiology of inflammatory bowel disease, myocarditis and neurovascular disease, and as novel targets for therapeutic management of several disease states.

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“…Further evidence comes from the cryolesion-enhanced form of cerebral EAE in which the removal of deep cervical lymph nodes during the incubation period of EAE and at the same time as the cerebral cryolesion significantly reduces the burden of EAE in the cerebral hemispheres [106]. Transfer of lymphocytes from animals with cryolesion-EAE resulted in EAE lesions that were predominantly in the cerebral hemispheres [73]. These results suggest that lymphocytes from donors with cryolesion-EAE target the brain in recipient animals in preference to the spinal cord.…”

Section: Relationships Between Lymphatic Drainage Of the Brain And Nementioning

confidence: 99%

Vascular, glial, and lymphatic immune gateways of the central nervous system

et al. 2016

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Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood–brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system. Recent developments in high-resolution imaging techniques have prompted a reassessment of the relationships between the CNS and the immune system. This review will take these developments into account in describing our present understanding of the anatomical connections of the CNS fluid drainage pathways towards regional lymph nodes and our current concept of immune cell trafficking into the CNS during immunosurveillance and neuroinflammation. Cerebrospinal fluid (CSF) and interstitial fluid are the two major components that drain from the CNS to regional lymph nodes. CSF drains via lymphatic vessels and appears to carry antigen-presenting cells. Interstitial fluid from the CNS parenchyma, on the other hand, drains to lymph nodes via narrow and restricted basement membrane pathways within the walls of cerebral capillaries and arteries that do not allow traffic of antigen-presenting cells. Lymphocytes targeting the CNS enter by a two-step process entailing receptor-mediated crossing of vascular endothelium and enzyme-mediated penetration of the glia limitans that covers the CNS. The contribution of the pathways into and out of the CNS as initiators or contributors to neurological disorders, such as multiple sclerosis and Alzheimer’s disease, will be discussed. Furthermore, we propose a clear nomenclature allowing improved precision when describing the CNS-specific communication pathways with the immune system.

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Lymphocyte targeting of the brain in adoptive transfer cryolesion-EAE

Cited by 55 publications

References 29 publications

Transfer of Central Nervous System Autoantigens and Presentation in Secondary Lymphoid Organs

Transfer of Central Nervous System Autoantigens and Presentation in Secondary Lymphoid Organs

Anatomy and roles of lymphatics in inflammatory diseases

Vascular, glial, and lymphatic immune gateways of the central nervous system

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