Hyper-reactive cloned mice generated by direct nuclear transfer of antigen-specific CD4+ T cells

T-cell receptor (TCR)-transgenic mice have been employed for evaluating antigen-response mechanisms, but their non-endogenous TCR might induce immune response differently than the physiologically expressed TCR. Nuclear transfer cloning produces animals that retain the donor genotype in all tissues including germline and immune systems. Taking advantage of this feature, we generated cloned mice that carry endogenously rearranged TCR genes from antigen-specific CD4(+) T cells. We show that T cells of the cloned mice display distinct developmental pattern and antigen reactivity because of their endogenously pre-rearranged TCR alpha (rT alpha) and TCR beta (rT beta) alleles. These alleles were transmitted to the offspring, allowing us to establish a set of mouse lines that show chronic-type allergic phenotypes, that is, bronchial and nasal inflammation, upon local administrations of the corresponding antigens. Intriguingly, the existence of either rT alpha or rT beta is sufficient to induce in vivo hypersensitivity. These cloned mice expressing intrinsic promoterregulated antigen-specific TCR are a unique animal model with allergic predisposition for investigating CD4(+) T-cell-mediated pathogenesis and cellular commitment in immune diseases.