Jang Myoung Ho, Kweon Mi Na, Hiroi Takachika, Yamamoto Masafumi, Takahashi Ichiro, Kiyono Hiroshi
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, 565-0871, Osaka, Japan.
Vaccine. 2003 Apr 2;21(15):1613-9. doi: 10.1016/s0264-410x(02)00734-x.
Cholera toxin (CT), a powerful mucosal adjuvant, is a potent inducer of Th2-type responses via activation of co-stimulatory molecules for the induction of IgA antibody responses. Less appreciated is the ability of CT to induce and regulate cytotoxic T lymphocyte (CTL) responses. In order to help for clarifying mechanisms underlying the CTL-inducing ability of CT, we have examined the effects of CT on dendritic cells (DCs) that could lead to the induction of cytotoxic CD8(+) T cells. When bone marrow-derived DCs (BM-DCs) were cultured with CT in vitro, B7-1 but not B7-2 molecules were significantly enhanced and allogenic CTL responses were induced. Also, increased numbers of IFN-gamma-secreting CD8(+) T cells were elicited when CT-treated BM-DCs were co-cultured with allogenic CD8(+) CTLs. Antibody blockade of B7-1 on CT-treated BM-DCs suppressed allogenic CTL responses, further indicating the importance of CT-induced B7-1 molecules on DCs for the acquisition of cytolytic function by CTL precursors. CD40 signaling was proven not necessary for the CT-induced CTL response since CT-treated CD40(-/-) BM-DCs developed CTL responses equivalent to those detected in CT-treated BM-DCs derived from normal mice. Our results suggest that CT-treated DCs are effective inducers of CD8(+) CTL, and this induction is mediated through CT's ability to enhance B7-1 expression on DCs.
霍乱毒素（CT）是一种强大的黏膜佐剂，通过激活共刺激分子诱导IgA抗体反应，是Th2型反应的有效诱导剂。CT诱导和调节细胞毒性T淋巴细胞（CTL）反应的能力却较少受到关注。为了有助于阐明CT诱导CTL能力的潜在机制，我们研究了CT对可导致细胞毒性CD8(+) T细胞诱导的树突状细胞（DC）的影响。当体外将骨髓来源的DC（BM-DC）与CT一起培养时，B7-1分子而非B7-2分子显著增强，并且诱导了同种异体CTL反应。此外，当用CT处理的BM-DC与同种异体CD8(+) CTL共培养时，分泌IFN-γ的CD8(+) T细胞数量增加。对用CT处理的BM-DC上的B7-1进行抗体阻断可抑制同种异体CTL反应，进一步表明CT诱导的DC上的B7-1分子对于CTL前体获得溶细胞功能的重要性。由于用CT处理的CD40(-/-) BM-DC产生的CTL反应与正常小鼠来源的用CT处理的BM-DC中检测到的反应相当，因此证明CD40信号对于CT诱导的CTL反应不是必需的。我们的结果表明，用CT处理的DC是CD8(+) CTL的有效诱导剂，并且这种诱导是通过CT增强DC上B7-1表达的能力介导的。
