Shimizu J, Zou J P, Ikegame K, Katagiri T, Fujiwara H, Hamaoka T
Biomedical Research Center, Osaka University Medical School, Japan.
J Immunol. 1991 Mar 1;146(5):1708-14.
Spleen cells of BALB/c mice bearing a syngeneic CSA1M fibrosarcoma were treated with anti-Thy-1.2 antibody plus C, yielding a T cell-depleted, APC-containing fraction. The APC-containing fraction was first tested for its capacity to present exogenous modified-self or another tumor (Meth A) Ag after in vitro pulsing. The results showed comparable Ag-presenting capacities to those obtained by APC-containing fraction from normal spleen cells, indicating that APC function is not affected in tumor-bearing mice. We next examined whether APC from CSA1M-bearing mice bind endogenously generated CSA1M tumor Ag onto its surfaces to stimulate tumor-specific T cells. Five rounds of inoculation of APC-containing fraction from CSA1M-bearing mice without further in vitro pulsing resulted in the induction of potent anti-CSA1M immune resistance. The involvement of anti-CSA1M T cells in the induction of anti-CSA1M immunity was excluded by the fact that the in vivo immunity was excluded by the fact that the in vivo immunity was delivered by Thy-1+ cell-depleted, but not by Thy-1+ cell-enriched fractions of spleen cells from CSA1M-bearing mice. Moreover, the failure of Sephadex G10-passed spleen cells to deliver anti-CSA1M resistance demonstrated the absolute requirement of APC for inducing the in vivo immunity. Finally, this in vivo resistance was found to be tumor specific, because APC fractions from CSA1M-bearing and Meth A-bearing BALB/c mice induced immune resistance selective against the corresponding tumor cell challenge. These results indicate that APC from tumor-bearing hosts can not only exert unaffected APC function against exogenous Ag, but also function to present tumor Ag generated endogenously in the tumor-bearing state and to produce tumor-specific immunity in vivo.
用抗Thy-1.2抗体加补体处理携带同基因CSA1M纤维肉瘤的BALB/c小鼠的脾细胞，得到一个T细胞耗竭但含抗原呈递细胞（APC）的组分。首先检测该含APC的组分在体外脉冲处理后呈递外源性修饰自身或另一种肿瘤（Meth A）抗原的能力。结果显示其抗原呈递能力与从正常脾细胞获得的含APC组分相当，表明荷瘤小鼠的APC功能未受影响。接下来，我们研究了来自携带CSA1M小鼠的APC是否将内源性产生的CSA1M肿瘤抗原结合到其表面，以刺激肿瘤特异性T细胞。对来自携带CSA1M小鼠的含APC组分进行五轮接种，无需进一步体外脉冲处理，结果诱导出了强大的抗CSA1M免疫抗性。来自携带CSA1M小鼠的脾细胞中Thy-1+细胞耗竭而非Thy-1+细胞富集的组分可在体内产生免疫，这一事实排除了抗CSA1M T细胞参与抗CSA1M免疫诱导的可能性。此外，经Sephadex G10柱过滤的脾细胞未能产生抗CSA1M抗性，这表明诱导体内免疫绝对需要APC。最后，发现这种体内抗性具有肿瘤特异性，因为来自携带CSA1M和携带Meth A的BALB/c小鼠的APC组分诱导的免疫抗性对相应的肿瘤细胞攻击具有选择性。这些结果表明，来自荷瘤宿主的APC不仅能对外源性抗原发挥未受影响的APC功能，还能呈递在荷瘤状态下内源性产生的肿瘤抗原，并在体内产生肿瘤特异性免疫。
