アクティブボード・２００８年　9月
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研究発表を行った学会；
・第９回熊本エイズセミナー.
　平成２０年９月１８日～１９日(熊本)

タイトル；Different effects of HIV-1-specific CTLs having a strong ability to suppress HIV-1 replication on selection of escape mutant viruses.
　
発表者；　小泉　寛和　氏
　　　（熊本大学　エイズ学研究センター　ウイルス制御分野）
Abstract；
HIV-1 escape mutants are well known to be selected by immune pressure via HIV-1-specific CTLs and anti-HIV-1 neutralizing antibodies. However, it still remains unknown what kinds of HIV-1-specific CTLs and neutralizing antibodies select the escape mutants. The ability of the CTLs to suppress HIV-1 replication is assumed to be associated with the selection of escape mutants from the CTLs. We here investigated relationship between the ability of HLA-A*1101-restricted 3 HIV-1-specific CTLs, which were dominantly induced in HIV-1-infected individuals, to suppress HIV-1 replication in vitro and the appearance of escape mutations on CTL epitopes in HIV-1-infected individuals. In the results, both of Nef73- and Nef84-specific CTLs had a strong ability to suppress HIV-1 replication. On the other hand, Gag349-specific CTLs had a weak ability to suppress HIV-1 replication. And only Nef84-specific CTLs selected the escape mutant. Therefore, there was no correlation between the ability of these CTLs to suppress HIV-1 replication in vitro and the appearance of escape mutants, furthermore it is suggested that Nef73-specific CTLs was functionally exhausted in vivo. Recently, it was reported that PD-1 expression on HIV-1-specific T cells was associated with dysfunction of the T cells. Indeed, to clarify whether Nef73-specific CTLs was functionally exhausted in vivo, we analyzed PD-1 expression on both of Nef73- and Nef84-specific CTLs from PBMCs of HIV-1-infected individuals. Nef73-specific CTLs expressed a significantly higher level of PD-1 than Nef84-specific ones. Similar findings were found for other HLA-restricted CTLs having a strong ability to suppress HIV-1 replication. These results suggest that both the ability of these CTLs to suppress HIV-1 replication and PD-1 expression on these CTLs are crucial factors in the selection of escape mutations in vivo．