Lymphocytes from SJL/J mice immunized with spinal cord respond selectively to a peptide of proteolipid protein and transfer relapsing demyelinating experimental autoimmune encephalomyelitis.

Abstract

Relapsing experimental autoimmune encephalomyelitis (R-EAE) can be induced in SJL/J mice by immunization with spinal cord homogenate and adjuvant. The specific Ag(s) responsible for acute disease and subsequent relapses in this model is unknown. Myelin basic protein (BP), an encephalitogenic peptide of BP (BP 87-99), and proteolipid protein (PLP) can each induce R-EAE in SJL/J mice, and a peptide of PLP (PLP 139-151) has been reported to induce acute EAE. To determine the encephalitogens in cord-immunized mice with R-EAE, the in vitro proliferative responses of lymph node cells (LNC) and central nervous system mononuclear cells to BP, BP peptides, and PLP peptides were examined during acute EAE and during relapses. LNC responded only to PLP peptides 139-151 and 141-151 and did not respond to BP or its peptides during acute or chronic disease. Central nervous system mononuclear cells also preferentially responded to PLP 139-151 and 141-151 during acute and relapsing disease. A PLP 139-151 peptide-specific Th cell line was selected from LNC of cord-immunized donors. Five million peptide-specific line cells transferred severe relapsing demyelinating EAE to naive recipients. We conclude that PLP peptide 139-151 is the major encephalitogen for R-EAE in cord-immunized SJL/J mice. We demonstrate for the first time that Th cells specific for this peptide are sufficient to transfer relapsing demyelinating EAE. The predominance of a PLP immune response rather than a BP response in SJL/J mice suggests that genetic background may determine the predominant myelin Ag response in human demyelinating diseases such as multiple sclerosis.

Role of omega-3 endocannabinoids in the modulation of T-cell activity in a multiple sclerosis experimental autoimmune encephalomyelitis (EAE) model

“…These data collectively suggest that DHEA is acting to suppress the immune response. Considering that RR-EAE is a CD4 + T-cell-mediated process ( 71 , 72 ), these in vivo data correspond with our findings that DHEA and DHEA-epoxide eCBs influence T-cell polarization, Th17 effector function, and antigen-specific activation in TCR MOG splenocytes. Flow cytometry analysis did not indicate any differences in the IFNγ- or IL17—producing T-cells in the brain of our first study RR-EAE study ( Fig.…”

Arginine vasopressin hormone receptor antagonists in experimental autoimmune encephalomyelitis rodent models: A new approach for human multiple sclerosis treatment

“…Some studies used the SJL/J mice to replicate the MS disease. In 1991, Whitham et al (1991) developed a relapsing EAE model using MBP and PLP (PLP139-151) in CFA to induce acute EAE at 9–12 days post-inoculation, suggesting that the background of a biological model may be a predominant factor in myelin Ag response in patients with MS. The classification of clinical signs in EAE models is described by the progressive weakness in the extremities, beginning with a loss of tail tone, followed by the limp tail and hind leg weakness, and subsequently resulting in a limp tail and complete paralysis of the hind legs.…”