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Marked Increase in Number of Dendritic Cells in Autoimmune-Prone (NZW x BXSB)F1 Mice with Age

^a First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka;
^b Department of Biotechnology, Kyoto Institute of Technology, Sakyo-ku, Kyoto;
^c Third Department of Internal Medicine, Kansai Medical University, Moriguchi City, Osaka;
^d First Department of Internal Medicine, Kansai Medical University, Moriguchi City, Osaka;
^e Second Department of Internal Medicine, Kansai Medical University, Moriguchi City, Osaka, Japan

Key Words. Autoimmune disease • Dendritic cell • Flt-3 ligand • (NZW x BXSB)F1 mouse

Susumu Ikehara, M.D., Ph.D., First Department of Pathology, Kansai Medical University, Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan. Telephone: 81-6-6993-9429; Fax: 81-6-6994-8283; e-mail: ikehara{at}takii.kmu.ac.jp

Here, we report that the number of CD11c⁺CD3^– B220^– cells increases in autoimmune-prone male (NZW x BXSB)F1 (W/BF1) mice with age. The CD11c⁺CD3^–B220^– cells from W/BF1 mice show a typical stellate shape and induce the proliferation of T cells. In the CD11c⁺CD3^–B220^– cells from W/BF1 mice, CD11b (Mac-1), NK 1.1, and CD95 (Fas) are upregulated in comparison with normal mice, while the expression of CD8, CD117 (c-kit), CD135 (Flk-2/Flt-3), and Sca-1 decreases. There is a significant increase in Flt-3L (FL) mRNA in the bone marrow of W/BF1 mice with age. Moreover, activated hemopoietic cells express high levels of FL. The injection of CD11c⁺CD3^–B220^– cells from old W/BF1 mice to young W/BF1 mice transiently induces autoimmune disease (thrombocytopenia). These results suggest that hyperproduction of FL from activated hemopoietic cells induces a dramatic increase in the number of dendritic cells in aged W/BF1 mice, followed by the acceleration of autoimmunity.

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