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Soluble peptide treatment reverses CD8 T-cell-induced disease in a mouse model of spontaneous tissue-selective autoimmunity.

ABSTRACT: Transgenic (Tg) mouse models of autoimmunity have been used to express model antigens that can be recognized by T cells or by autoantibodies. To identify mechanisms of CD8-mediated tissue-specific autoimmune reactions and to identify potential treatments, we generated a double-transgenic (DTg) murine model of autoimmunity by crossing keratin-14 (K14)-soluble chicken ovalbumin (sOVA) mice, which express sOVA predominantly in external ear skin, with OT-I mice whose CD8 T cells express V?2/V?5 regions of the TCR and are specific for SIINFEKL peptide (chicken ovalbumin (OVA) peptide 257-264) in association with class I major histocompatibility complex. The K14-sOVA/OT-I DTg mice develop a destructive process selectively targeting the external ear pinnae in the first 6 days of life. The ear bud area develops an intense inflammatory infiltrate of OT-I cells. Administration of the SIINFEKL peptide intravenously to pregnant F1 (filial 1, first filial generation of animal offspring from cross-mating two parental types) mice and subsequently intraperitoneally to newborn pups resulted in normal external ear development. Treatment with this self-peptide markedly reduced OT-I cell numbers, as well as downregulated the CD8 co-receptor. This model can be useful in studying localized, tissue-specific, immune-mediated skin disease, and provide information about potential therapies for autoimmune diseases in which specific molecular targets are known.

SUBMITTER: Paek SY

PROVIDER: S-EPMC3395362 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Soluble peptide treatment reverses CD8 T-cell-induced disease in a mouse model of spontaneous tissue-selective autoimmunity.

Paek So Yeon SY Miyagawa Fumi F Zhang Hong H Linton Jay T JT Hoover Shelley B SB Simpson R Mark RM Katz Stephen I SI

The Journal of investigative dermatology 20111117 3 Pt 1

Transgenic (Tg) mouse models of autoimmunity have been used to express model antigens that can be recognized by T cells or by autoantibodies. To identify mechanisms of CD8-mediated tissue-specific autoimmune reactions and to identify potential treatments, we generated a double-transgenic (DTg) murine model of autoimmunity by crossing keratin-14 (K14)-soluble chicken ovalbumin (sOVA) mice, which express sOVA predominantly in external ear skin, with OT-I mice whose CD8 T cells express Vα2/Vβ5 regi ...[more]

PMID: 22089830

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Dataset Information

Soluble peptide treatment reverses CD8 T-cell-induced disease in a mouse model of spontaneous tissue-selective autoimmunity.

Publications

Soluble peptide treatment reverses CD8 T-cell-induced disease in a mouse model of spontaneous tissue-selective autoimmunity.

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