Akiyama M, Bean M A, Sadamoto K, Takahashi Y, Brankovan V
J Immunol. 1983 Dec;131(6):3085-90.
The question as to whether or not cancer patients have "tumor antigen"-induced suppressor T cells is of considerable interest and importance. As an approach to that question, the effect of addition of autologous irradiated tumor-derived cells (TDC) on the mixed lymphocyte response (MLR) of patients' lymphocytes (Ly) and of healthy donor Ly was tested. The rationale for these experiments was based on the fact that circulating antigen-responsive blood lymphocytes can be reactivated in vitro by exposure to the appropriate antigen. Thus, if there are circulating tumor "antigen"-reactive suppressor Ly, exposure to TDC as a source of the antigen should reactivate those cells. Reactivation of suppressor cells might result in diminished responsiveness to other stimuli such as alloantigens in the mixed leukocyte culture. We found that the addition of TDC to Ly cultures produced four distinct patterns of reaction. In 26 of the 74 different patient-tumor assays, the addition of autologous TDC to the patient cultures inhibited MLR, but the addition of the same TDC to cultures of Ly from healthy donors had no effect or increased their responsiveness (Specific Suppression). In 21 cases, the addition of autologous TDC to the patient cultures suppressed the MLR and the addition of the same TDC to control cultures suppressed the response of some but not all the healthy donors (Selective Suppression). In four cases, the addition of TDC to the cultures suppressed the MLR of the patients and all of the control donors (Nonspecific Suppression). In 23 cases, the addition of autologous TDC resulted in no suppression of the patient MLR or of any of the simultaneously tested normal donors (No Suppression). When TDC of patients with noninvasive bladder cancer were added to their own Ly cultures, only four of 11 produced specific or selective suppression compared to 11 of 12 when TDC came from patients with superficially invasive cancer. These data provide indirect evidence to support the hypothesis that human tumors induce circulating suppressor cells that may be reactivated in vitro by co-culture with TDC.
癌症患者是否拥有“肿瘤抗原”诱导的抑制性T细胞这一问题备受关注且具有重要意义。作为探讨该问题的一种方法，研究人员测试了添加自体照射的肿瘤衍生细胞（TDC）对患者淋巴细胞（Ly）以及健康供体Ly的混合淋巴细胞反应（MLR）的影响。这些实验的理论依据基于以下事实：循环中的抗原反应性血液淋巴细胞可通过暴露于适当抗原在体外被重新激活。因此，如果存在循环中的肿瘤“抗原”反应性抑制性Ly，那么将其暴露于作为抗原来源的TDC应该会重新激活这些细胞。抑制性细胞的重新激活可能会导致对其他刺激（如混合白细胞培养中的同种异体抗原）的反应性降低。我们发现，向Ly培养物中添加TDC会产生四种不同的反应模式。在74种不同的患者-肿瘤检测中，有26种情况下，向患者培养物中添加自体TDC会抑制MLR，但向健康供体的Ly培养物中添加相同的TDC则没有效果或会增加其反应性（特异性抑制）。在21种情况下，向患者培养物中添加自体TDC会抑制MLR，而向对照培养物中添加相同的TDC会抑制部分而非全部健康供体的反应（选择性抑制）。在4种情况下，向培养物中添加TDC会抑制患者以及所有对照供体的MLR（非特异性抑制）。在23种情况下，添加自体TDC不会抑制患者的MLR或任何同时检测的正常供体的MLR（无抑制）。当将非侵袭性膀胱癌患者的TDC添加到他们自己的Ly培养物中时，11例中只有4例产生了特异性或选择性抑制，而当TDC来自浅表侵袭性癌症患者时，12例中有11例产生了特异性或选择性抑制。这些数据提供了间接证据，支持了人类肿瘤诱导循环抑制性细胞的假说，这些抑制性细胞可能通过与TDC共培养在体外被重新激活。
