Research Article| Volume 38, ISSUE 1, P17-24, April 2005

Analysis of T cell receptor (TCR) BV-gene clonotypes in NC/Nga mice developing dermatitis resembling human atopic dermatitis



      Our previous study showed that T cells in skin lesions of human atopic dermatitis (AD) had oligoclonal accumulation, indicating the involvement of antigen-specific immune reactions at those sites. Recently, NC/Nga mice, which develop skin lesions similar to AD, have been proposed as a model for that disease.


      To clarify whether NC/Nga mice are suitable as a model for human AD from the viewpoint of their antigen-specific immune responses.


      Reverse transcription-polymerase chain reaction (RT-PCR) and single strand conformation polymorphism (SSCP) analyses were conducted to detect TCR BV genes of clonally expanded T cells derived from NC/Nga mice at an early phase of the AD-like dermatitis, at a late phase of the dermatitis, and with no AD-like dermatitis.


      (1) T cells with TCR BV 7, 10 and 17 reside in the skin of NC/Nga mice without the AD-like dermatitis. (2) T cells with these BV genes contain oligoclonal accumulations, however, expanded T cell clonotypes are also detected in the spleen and exist constantly during the course of the AD-like dermatitis. (3) Development of the AD-like dermatitis is associated with additional oligoclonal expansion/accumulation of T cells with TCR BV 2, 4 and 6 genes. (4) Progression of the AD-like dermatitis is associated with further oligoclonal expansion/accumulation of T cells with the TCR BV 14 gene. (5) Some of the expanded TCR clonotypes are common between the individual mice and between early and late phases.


      Taking these data together with the previous human AD studies, NC/Nga mice seem to be an appropriate model for human AD.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Dermatological Science
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Leung D.Y.
        • Bhan A.K.
        • Schneeberger E.E.
        • Geha R.S.
        Characterization of the mononuclear cell infiltrate in atopic dermatitis using monoclonal antibodies.
        J Allergy Clin Immunol. 1983; 71: 47-56
        • Menssen A.
        • Trommler P.
        • Vollmer S.
        • Schendel D.
        • Albert E.
        • Gurtler L.
        • et al.
        Evidence for an antigen-specific cellular immune response in skin lesions of patients with psoriasis vulgaris.
        J Immunol. 1995; 155: 4078-4083
        • Mihm Jr., M.C.
        • Soter N.A.
        • Dvorak H.F.
        • Austen K.F.
        The structure of normal skin and the morphology of atopic eczema.
        J Invest Dermatol. 1976; 67: 305-312
        • Takahama H.
        • Masuko-hongo K.
        • Tanaka A.
        • Kawa Y.
        • Ohta N.
        • Yamamoto K.
        • et al.
        T-cell clonotypes specific for Dermatophagoides pteronyssinus in the skin lesions of patients with atopic dermatitis.
        Hum Immunol. 2002; 63: 558-566
        • Tanaka A.
        • Takahama H.
        • Kato T.
        • Kubota Y.
        • Kurokawa K.
        • Nishioka K.
        • et al.
        Clonotypic analysis of T cells infiltrating the skin of patients with atopic dermatitis: evidence for antigen-driven accumulation of T cells.
        Hum Immunol. 1996; 48: 107-113
        • Matsuoka H.
        • Maki N.
        • Yoshida S.
        • Arai M.
        • Wang J.
        • Oikawa Y.
        • et al.
        A mouse model of the atopic eczema/dermatitis syndrome by repeated application of a crude extract of house-dust mite Dermatophagoides farinae.
        Allergy. 2003; 58: 139-145
        • Aioi A.
        • Tonogaito H.
        • Suto H.
        • Hamada K.
        • Ra C.R.
        • Ogawa H.
        • et al.
        Impairment of skin barrier function in NC/Nga Tnd mice as a possible model for atopic dermatitis.
        Br J Dermatol. 2001; 144: 12-18
        • Matsuda H.
        • Watanabe N.
        • Geba G.P.
        • Sperl J.
        • Tsudzuki M.
        • Hiroi J.
        • et al.
        Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC/Nga mice.
        Int Immunol. 1997; 9: 461-466
        • Matsumoto M.
        • Ra C.
        • Kawamoto K.
        • Sato H.
        • Itakura A.
        • Sawada J.
        • et al.
        IgE hyperproduction through enhanced tyrosine phosphorylation of Janus kinase 3 in NC/Nga mice, a model for human atopic dermatitis.
        J Immunol. 1999; 162: 1056-1063
        • Kato T.
        • Ikeda Y.
        • Zong Z.P.
        • Sasakawa H.
        • Kurokawa M.
        • Masuko K.
        • et al.
        Characterization of T cell receptor beta chains of accumulating T cells in skin allografts in mice.
        Transplantation. 1996; 62: 266-272
        • Yamamoto K.
        • Masuko-Hongo K.
        • Tanaka A.
        • Kurokawa M.
        • Hoeger T.
        • Nishioka K.
        • et al.
        Establishment and application of a novel T cell clonality analysis using single-strand conformation polymorphism of T cell receptor messenger signals.
        Hum Immunol. 1996; 48: 23-31
        • Yamamoto K.
        • Sakoda H.
        • Nakajima T.
        • Kato T.
        • Okubo M.
        • Dohi M.
        • et al.
        Accumulation of multiple T cell clonotypes in the synovial lesions of patients with rheumatoid arthritis revealed by a novel clonality analysis.
        Int Immunol. 1992; 4: 1219-1223
        • Barth R.K.
        • Kim B.S.
        • Lan N.C.
        • Hunkapiller T.
        • Sobieck N.
        • Winoto A.
        • et al.
        The murine T-cell receptor uses a limited repertoire of expressed V beta gene segments.
        Nature. 1985; 316: 517-523
        • Behlke M.A.
        • Spinella D.G.
        • Chou H.S.
        • Sha W.
        • Hartl D.L.
        • Loh D.Y.
        T-cell receptor beta-chain expression: dependence on relatively few variable region genes.
        Science. 1985; 229: 566-570
        • Goverman J.
        • Minard K.
        • Shastri N.
        • Hunkapiller T.
        • Hansburg D.
        • Sercarz E.
        • et al.
        Rearranged beta T cell receptor genes in a helper T cell clone specific for lysozyme: no correlation between V beta and MHC restriction.
        Cell. 1985; 40: 859-867
        • Chou H.S.
        • Anderson S.J.
        • Louie M.C.
        • Godambe S.A.
        • Pozzi M.R.
        • Behlke M.A.
        • et al.
        Tandem linkage and unusual RNA splicing of the T-cell receptor beta-chain variable-region genes.
        Proc Natl Acad Sci USA. 1987; 84: 1992-1996
        • Saito H.
        • Kranz D.M.
        • Takagaki Y.
        • Hayday A.C.
        • Eisen H.N.
        • Tonegawa S.
        Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences.
        Nature. 1984; 309: 757-762
        • Behlke M.A.
        • Chou H.S.
        • Huppi K.
        • Loh D.Y.
        Murine T-cell receptor mutants with deletions of beta-chain variable region genes.
        Proc Natl Acad Sci USA. 1986; 83: 767-771
        • Kappler J.W.
        • Wade T.
        • White J.
        • Kushnir E.
        • Blackman M.
        • Bill J.
        • et al.
        A T cell receptor V beta segment that imparts reactivity to a class II major histocompatibility complex product.
        Cell. 1987; 49: 263-271
        • Opelz G.
        • Kiuchi M.
        • Takasugi M.
        • Terasaki P.I.
        Autologous stimulation of human lymphocyte subpopulation.
        J Exp Med. 1975; 142: 1327-1333
        • Bergstresser P.R.
        • Tigelaar R.E.
        • Dees J.H.
        • Streilein J.W.
        Thy-1 antigen-bearing dendritic cells populate murine epidermis.
        J Invest Dermatol. 1983; 81: 286-288
        • Tamada Y.
        • Ohashi M.
        • Kobayashi T.
        • Yoshida T.
        • Kondo K.
        Pathological studies on NC mouse with erythema and alopecia.
        Jpn J Allergol. 1976; 25: 829-836