Adjuvant-guided type-1 and type-2 immunity: infectious/noninfectious dichotomy defines the class of response.
Adjuvant-guided type-1 and type-2 immunity: infectious/noninfectious dichotomy defines the class of response.
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DOI：
10.4049/jimmunol.162.7.3942
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发表时间：
1999-04
影响因子：
4.4
通讯作者：
H. C. Yip;A. Karulin;M. Tary‐Lehmann;Maike D. Hesse;H. Radeke;P. Heeger;R. Trezza;F. Heinzel;T. Forsthuber;P. Lehmann
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文献类型：
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作者：
H. C. Yip;A. Karulin;M. Tary‐Lehmann;Maike D. Hesse;H. Radeke;P. Heeger;R. Trezza;F. Heinzel;T. Forsthuber;P. Lehmann
传统上，蛋白质Ag已经在CFA（具有灭活分枝杆菌的油）中注射以诱导免疫，并且与IFA（单独的油）一起注射以诱导耐受。我们在这里报告，注射鸡蛋清溶菌酶，一个原型银，在CFA诱导和IFA诱导池的鸡蛋清溶菌酶特异性记忆T细胞的可比罚款的特异性，克隆大小，和亲合力谱，但与1型和2型细胞因子的签名，分别。在七种蛋白质Ag和总共六种小鼠品系中观察到这种几乎单极1型和2型免疫的免疫诱导。因此，高度极化的1型和2型免疫可通过选择佐剂容易地实现，而不管宿主的遗传偏好和蛋白质Ag的性质。这一发现对开发抗传染病和自身免疫性疾病的疫苗具有深远的意义。此外，我们的实验表明，用IFA注射的Ag对T细胞的免疫原性与CFA一样强，这表明分枝杆菌的存在并不决定通过第二信号连接启动幼稚T细胞，而是决定向表达1型或2型细胞因子的CD4记忆细胞下游分化的路径。
Traditionally, protein Ags have been injected in CFA (oil with inactivated mycobacteria) to induce immunity and with IFA (oil alone) to induce tolerance. We report here that injection of hen eggwhite lysozyme, a prototypic Ag, in CFA-induced and IFA-induced pools of hen eggwhite lysozyme-specific memory T cells of comparable fine specificity, clonal size, and avidity spectrum, but with type-1 and type-2 cytokine signatures, respectively. This adjuvant-guided induction of virtually unipolar type-1 and type-2 immunity was observed with seven protein Ags and in a total of six mouse strains. Highly polarized type-1 and type-2 immunity are thus readily achievable through the choice of adjuvant, irrespective of the genetic bias of the host and of the nature of the protein Ag. This finding should have far-reaching implications for the development of vaccines against infectious and autoimmune diseases. Furthermore, our demonstration that Ag injected with IFA is as strongly immunogenic for T cells as it is with CFA shows that the presence of the mycobacteria determines not the priming of naive T cells through the second-signal link but the path of downstream differentiation toward CD4 memory cells that express either type-1 or type-2 cytokines.