Gender differences in CNS autoimmunity induced by mimicry epitope for PLP 139–151 in SJL mice

Abstract

Development of multiple sclerosis (MS) is more prevalent in females than in males, but the underlying mechanisms are not clear. Microbial infections have been suspected as triggers of MS and it is not known whether gender differences in reactivity to environmental antigens contribute to the disease pathogenesis. We demonstrated that ACA 83-95, a mimicry epitope from Acanthamoeba castellanii for proteolipid protein (PLP) 139-151, induces clinical signs of encephalomyelitis in both male and female SJL mice. Conversely ACA 83-95-induced effector cells from males fail to induce disease in female mice. Although we found no gender differences in the frequencies of antigen-specific cells including cytokine production, PLP-specific cells induced with ACA 83-95 differed in T cell receptor vβ usage from those induced with PLP 139-151. The data suggest that cross-reactive T cell expansion occurs similarly in both males and females, but their disease-inducing ability is influenced by gender.

Autoimmunity in the Mediation of Granulomatous Amoebic Encephalitis: Implications for Therapy

“…On the contrary, the pathogenic potential of effector T cells is directly tested in AT-EAE protocol by transferring antigen-stimulated lymph node or spleen cells generated from previously immunized mice, thus eliminating the need to immunize naive recipients prior to disease induction. Figure 3a shows that SJL mice immunized with ACA 83-95 developed clinical signs of EAE reminiscent of disease induced by the cognate peptide PLP 139-151 (Tuohy, et al, 1989, Massilamany, et al, 2010, Massilamany, et al, 2011. Verification of these results in AT-EAE protocol clearly indicated that the disease-induction by ACA 83-95 requires the mediation of antigen-sensitized T cells (Fig.…”

“…2; Massilamany, et al, 2010, Massilamany, et al, 2011. The epitope termed, ACA 83-95 is derived from rhodaneserelated sulfur transferase of Acanthamoeba.…”

“…The epitope termed, ACA 83-95 is derived from rhodaneserelated sulfur transferase of Acanthamoeba. We tested the disease-inducing ability of ACA 83-95 in the mouse model of experimental autoimmune encephalomyelitis (EAE), which has been traditionally used to study the pathophysiology of multiple sclerosis (MS) in humans (Massilamany, et al, 2010, Massilamany, et al, 2011. (Massilamany, et al, 2010, Massilamany, et al, 2011 We verified the encephalitogenicity of mimicry epitope in both active immunization and adoptive transfer (AT) EAE protocols in autoimmune-prone SJL mice bearing the H-2 s haplotype.…”

“…We tested the disease-inducing ability of ACA 83-95 in the mouse model of experimental autoimmune encephalomyelitis (EAE), which has been traditionally used to study the pathophysiology of multiple sclerosis (MS) in humans (Massilamany, et al, 2010, Massilamany, et al, 2011. (Massilamany, et al, 2010, Massilamany, et al, 2011 We verified the encephalitogenicity of mimicry epitope in both active immunization and adoptive transfer (AT) EAE protocols in autoimmune-prone SJL mice bearing the H-2 s haplotype. While EAE induction by active immunization requires administration of peptides emulsified in complete Freund's adjuvant (CFA), AT-EAE involves infusion of antigen-sensitized cells into naïve recipients (Miller & Karpus, 2007).…”

“…EAE induction by adoptive transfer. Short-term T cell lines were derived from mice immunized with the indicated peptides and viable lymphoblasts were injected into naive SJL mice intraperitoneally, and the mice were monitored for signs of EAE and scored (Massilamany, et al, 2010, Massilamany, et al, 2011. Scoring scale: 0, healthy; 1, limp tail or hind limb weakness, but not both; 2, limp tail and hind limb weakness; 3, partial paralysis of hind limbs; 4, complete paralysis of hind limbs; 5, moribund or dead (Tuohy, et al, 1989, Massilamany, et al, 2010, Massilamany, et al, 2011.…”