マラリア感染と治療を繰り返すことにより制御性のCD19陽性B細胞が生じ実験的脳マラリアの発症が抑制される

In African endemic area, adults are less vulnerable to cerebral malaria than children probably because of acquired partial immunity or semi-immune status. Here, we developed an experimental cerebral malaria (ECM) model for semi-immune mice. C57BL/6 (B6) mice underwent one, two and three cycles of infection and radical treatment (1-cure, 2-cure and 3-cure, respectively) before being finally challenged with 104 Plasmodium berghei ANKA without treatment. Our results showed that 100% of naive (0-cure), 67% of 1-cure, 37% of 2-cure and none of 3-cure mice succumbed to ECM within 10 days post challenge infection. In the protected 3-cure mice, significantly higher levels of plasma IL-10 and lower levels of IFN-γ than the others on day 7 post challenge infection were observed. Major increased lymphocyte subset of IL-10 positive cells in 3-cure mice was CD5(?)CD19(+) B cells. Passive transfer of splenic CD19(+) cells from 3-cure mice protected naive mice from ECM. Additionally, aged 3-cure mice were also protected from ECM 12 and 20 months after the last challenge infection. In conclusion, mice became completely resistant to ECM after three exposures to malaria. CD19(+) B cells are determinants in protective mechanism of semi-immune mice against ECM possibly via modulatory IL-10 for pathogenic IFN-γ production.長崎大学学位論文 学位記番号:博(医歯薬)甲第611号 学位授与年月日:平成25年8月7日Author： Lam Quoc Bao , Nguyen Tien Huy , Mihoko Kikuchi, Tetsuo Yanagi, Masachika Senba, Mohammed Nasir Shuaibu, Kiri Honma, Katsuyuki Yui, Kenji HirayamaCitation: PLoS ONE, 8(5), e64836; 201