Stoitzner Patrizia, Green Laura K, Jung Jae Y, Price Kylie M, Tripp Christoph H, Malissen Bernard, Kissenpfennig Adrien, Hermans Ian F, Ronchese Franca
Malaghan Institute of Medical Research, Wellington, New Zealand.
J Immunol. 2008 Feb 1;180(3):1991-8. doi: 10.4049/jimmunol.180.3.1991.
A role for Langerhans cells (LC) in the induction of immune responses in the skin has yet to be conclusively demonstrated. We used skin immunization with OVA protein to induce immune responses against OVA-expressing melanoma cells. Mice injected with OVA-specific CD8(+) T cells and immunized with OVA onto barrier-disrupted skin had increased numbers of CD8(+) T cells in the blood that produced IFN-gamma and killed target cells. These mice generated accelerated cytotoxic responses after secondary immunization with OVA. Prophylactic or therapeutic immunization with OVA onto barrier-disrupted skin inhibited the growth of B16.OVA tumors. LC played a critical role in the immunization process because depletion of LC at the time of skin immunization dramatically reduced the tumor-protective effect. The topically applied Ag was presented by skin-derived LC in draining lymph nodes to CD8(+) T cells. Thus, targeting of tumor Ags to LC in vivo is an effective strategy for tumor immunotherapy.
朗格汉斯细胞（LC）在皮肤免疫反应诱导过程中的作用尚未得到最终证实。我们采用卵清蛋白（OVA）蛋白进行皮肤免疫，以诱导针对表达OVA的黑色素瘤细胞的免疫反应。向小鼠注射OVA特异性CD8(+) T细胞，并在屏障破坏的皮肤上用OVA进行免疫，结果血液中产生γ干扰素并杀伤靶细胞的CD8(+) T细胞数量增加。这些小鼠在二次用OVA免疫后产生了加速的细胞毒性反应。在屏障破坏的皮肤上进行预防性或治疗性OVA免疫可抑制B16.OVA肿瘤的生长。LC在免疫过程中起关键作用，因为在皮肤免疫时去除LC会显著降低肿瘤保护作用。局部应用的抗原由引流淋巴结中源自皮肤的LC呈递给CD8(+) T细胞。因此，在体内将肿瘤抗原靶向LC是肿瘤免疫治疗的有效策略。
