Role of CD4⁺ T Cells in Allergic Airway Diseases: Learning from Murine Models

The essential contribution of CD4⁺ T cells in allergic airway diseases has been demonstrated, especially by using various murine models of antigen-induced airway inflammation. In addition to antigen-immunized mouse models employing mast cell-deficient mice and CD4⁺ T cell-depleting procedure, antigen-specific CD4⁺ T cell transfer models have revealed the possible development of allergic inflammation solely dependent on CD4⁺ T cells. Regardless of the classical Th1/Th2 theory, various helper T cell subsets have the potential to induce different types of allergic inflammation. T cell receptor (TCR)-transgenic (Tg) mice have been used for investigating T cell-mediated immune responses. Besides, we have recently generated cloned mice from antigen-specific CD4⁺ T cells through somatic cell nuclear transfer. In contrast to TCR-Tg mice that express artificially introduced TCR, the cloned mice express endogenously regulated antigen-specific TCR. Upon antigen exposure, the mite antigen-reactive T cell-cloned mice displayed strong airway inflammation accompanied by bronchial hyperresponsiveness in a short time period. Antigen-specific CD4⁺ T cell-cloned mice are expected to be useful for investigating the detailed role of CD4⁺ T cells in various allergic diseases and for evaluating novel anti-allergic drugs.