| Budget Amount *help |
¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1995: ¥4,300,000 (Direct Cost: ¥4,300,000)
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| Research Abstract |
CD40 is known to deliver an important costimulatory signal to B cells. CD23 is a low affinity receptor for IgE on lymphocytes. Both molecules have been suggested to play important roles in regulation of humoral and cell-mediated immune responses. To develop the experimental system and model mice for studying the immune system and immunological diseases, the mice deficient in CD40 or CD23 have been generated by gene targeting of embryonic stem cells. In CD40-deficient mice, Ig class switching and germinal center formation were severely impaired. The development of functional helper T cells was also affected in the absence of CD40. The CD40-deficient mice were susceptible to infection with the intracellular protozoan, Leishmania major because they failed to mount a T helper 1 response to parasites in the absence of CD40. By backcrossing the CD40-deficient into the type I diabetes model, NOD,we produced CD40-deficient NOD mice. CD40-deficient NOD never developed autoimmune insulitis and diabetes. These results demonstrate that CD40-deficient mice can be an ideal experimental model for infectious diseases as well as autoimmune diseases. In CD23-deficient mice, IgE antibody-mediated antigen focusing by antigen presenting cells was absent. CD23-deficient mice mounted higher levels of IgE responses when immunized with protein antigens, suggesting a possible role of CD23 in negative feedback in IgE production. Furthermore, experimental airway hyperresponsiveness is less severe in CD23-deficient mice than in wild-type littermates, indicating that CD23-deficient mice can be a experimental model to study the pathogenesis of asthma.
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