Successful treatment of EAE in rhesus monkeys with MHC class II specific monoclonal antibodies

Jonker, Margreet; Lambalgen, R. Van; Mitchell, Dennis J.; Durham, Stephen K.; Steinman, Lawrence

doi:10.1016/0896-8411(88)90064-9

Cited by 36 publications

(9 citation statements)

References 12 publications

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“…Anti-I-A treatment also reduced the number of relapses and mortality in chronic relapsing EAE (140). In rhesus monkeys treatment of paralytic disease was successful with polymorphic mouse anti-HLA-DQ or HLA DR antibodies that react with Rh-LAD (141). Therapy with monoclonal anti-class II antibodies is partially specific, only blocking responses restric ted by a given class-II isotype.…”

Section: Prevention and Treatment Of Eae With Anti-class II Antibodiesmentioning

confidence: 93%

The T Lymphocyte in Experimental Allergic Encephalomyelitis

Zamvil¹,

Steinman²

1990

Annu. Rev. Immunol.

955

428

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Section: Prevention and Treatment Of Eae With Anti-class II Antibodiesmentioning

confidence: 93%

The T Lymphocyte in Experimental Allergic Encephalomyelitis

Zamvil¹,

Steinman²

1990

Annu. Rev. Immunol.

955

428

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“…The APC-T-cell interaction is a well-known key effector of inflammatory injury in MS. A blockade of this interaction was shown to be effective in ameliorating EAE [34,35]. We demonstrated that SRA-deficient APCs had an impaired ability to drive to pro-inflammatory T-cell proliferation in response to MOG 35-55 and to drive production of cytokines that are known to play crucial roles in EAE, including IL-2, IL-17, IFN-γ, TNF-α and IL-6.…”

Section: Discussionmentioning

confidence: 85%

Expression of Scavenger receptor A on antigen presenting cells is important for CD4+ T-cells proliferation in EAE mouse model

Levy-Barazany¹,

Frenkel²

2012

J Neuroinflammation

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BackgroundMultiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by damage to the neuronal myelin sheath. One of the key effectors for inflammatory injury is the antigen-presenting cell (APC). The class A scavenger receptor (SRA), constitutively expressed by APCs, such as macrophages and dendritic cells in peripheral tissues and the CNS, was shown to play a role in the phagocytosis of myelin; however, the role of SRA in the development of experimental autoimmune encephalomyelitis (EAE) and autoimmune reaction in the periphery has not yet been studied.MethodsWe investigated EAE progression in wild-type (WT) vs. SRA−/− mice using clinical score measurements and characterized CNS pathology using staining. Furthermore, we assessed SRA role in mediating anti myelin pro-inflammatory response in cell cultures.ResultsWe discovered that EAE progression and CNS demyelination were significantly reduced in SRA−/− mice compared to WT mice. In addition, there was a reduction of infiltrating peripheral immune cells, such as T cells and macrophages, in the CNS lesion of SRA−/− mice, which was associated with reduced astrogliosis. Immunological assessment showed that SRA deficiency resulted in significant reduction of pro-inflammatory cytokines that play a major role in EAE progression, such as IL-2, IFN-gamma, IL-17 and IL-6. Furthermore, we discovered that SRA−/− APCs showed impairments in activation and in their ability to induce pro-inflammatory CD4+ T cell proliferation.ConclusionExpression of SRA on APCs is important for CD4+ T-cells proliferation in EAE mouse model. Further studies of SRA-mediated cellular pathways in APCs may offer useful insights into the development of MS and other autoimmune diseases, providing future avenues for therapeutic intervention.

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“…Experimental autoimmune encephalomyelitis (EAE) in the rhesus monkey has provided a valuable model for the study of multiple sclerosis (MS), a disease in which autoreactive T cells are involved in the destruction of the myelin in the central nervous system (Jonker et al 1988;Price et al 1988;Tsukada et al 1988;Jonker 1987a, 1987b). Interestingly, a preferential utilization of specific variable region families of the Tcr has been recently described in autoreactive T lymphocytes associated with EAE of a number of different species Burns et al 1989;Chluba et al 1989;Zamvil et al 1988).…”

Section: Discussionmentioning

confidence: 99%

Sequence and diversity of rhesus monkey T-cell receptor ? chain genes

1992

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We have sequenced 23 rearranged T-cell receptor beta chain (Tcrb) cDNA clones derived from peripheral blood lymphocytes (PBL) of a rhesus monkey. All of the clones have a variable-diversity-joining-constant (V-D-J-C) rearrangement similar to that of humans. Two rhesus constant (C) region genes were found, each closely resembling human Cb 1 and 2. All of the rhesus J region sequences align well with ten of the 13 reported human J regions. 17 of the 23 rhesus V region sequences could be assigned to families homologous with eight different human families (Vb 1, 2, 6, 7, 8, 9, 13, and 14). The remaining six V region sequences are more distantly related to human Vb 1 and 13. Thus, the organization and sequences of studied rhesus Tcrb chains resemble human homologs. An evolutionary tree analysis revealed paralogous relationships between specific members of the rhesus and human V region families. Analysis of synonymous and nonsynonymous nucleotide sequence differences indicated that the evolution of the presumed major histocompatibility complex (MHC)-contact regions of the Tcrb chains is less constrained than that of the framework regions.

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Successful treatment of EAE in rhesus monkeys with MHC class II specific monoclonal antibodies

Cited by 36 publications

References 12 publications

The T Lymphocyte in Experimental Allergic Encephalomyelitis

The T Lymphocyte in Experimental Allergic Encephalomyelitis

Expression of Scavenger receptor A on antigen presenting cells is important for CD4+ T-cells proliferation in EAE mouse model

Sequence and diversity of rhesus monkey T-cell receptor ? chain genes

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