Inglot A D, Gelder F, Georgiades J A
L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Biotherapy. 1998;11(1):27-37. doi: 10.1023/a:1007936706416.
We investigated possible mechanisms leading to the inhibition of the immune system in people with chronic disorders. Tumor cell produce protein released into the circulation, such as tumor associated antigens, may play an important role in processes preceding paralysis of the immune system. To test this hypothesis the following tumor associated antigens were used: AFP, OFP, CA-125, CA-50 and CA-19-9. Their role was assessed by modulating cytokine production in cord blood lymphocytes and peripheral white blood cells obtained from grown population of patients treated with colostrinin, an cytokine inducer. PHA, LPS and colostrinin were used as positive control in those essays. Each antigen tested individually induced IFN, TNF alpha and IL-6 in dose dependent fashion. None of the tested cytokines were spontaneously released by the cells. Data generated from these experiments indicated that tumor associated antigens are inducing type 1 cytokines in similar fashion as LPS or colostrinin. However, lymphocytes taken from patients undergoing therapy with colostrinin revealed progressive loss capability to produce type 1 cytokines as they did in case of colostrinin. The loss of the capability to respond to antigen may represent phenomenon leading to immune tolerance.
我们研究了导致慢性疾病患者免疫系统抑制的可能机制。肿瘤细胞产生释放到循环系统中的蛋白质,如肿瘤相关抗原,可能在免疫系统麻痹之前的过程中发挥重要作用。为了验证这一假设,使用了以下肿瘤相关抗原:甲胎蛋白(AFP)、癌胚纤维蛋白原(OFP)、癌抗原125(CA - 125)、癌抗原50(CA - 50)和癌抗原19 - 9(CA - 19 - 9)。通过调节从接受初乳素(一种细胞因子诱导剂)治疗的成年患者群体中获得的脐血淋巴细胞和外周血白细胞中的细胞因子产生来评估它们的作用。在这些实验中,植物血凝素(PHA)、脂多糖(LPS)和初乳素用作阳性对照。每种单独测试的抗原均以剂量依赖方式诱导干扰素(IFN)、肿瘤坏死因子α(TNFα)和白细胞介素 - 6(IL - 6)。所测试的细胞因子均未被细胞自发释放。这些实验产生的数据表明,肿瘤相关抗原以与LPS或初乳素类似的方式诱导1型细胞因子。然而,取自接受初乳素治疗患者的淋巴细胞显示出产生1型细胞因子的能力逐渐丧失,就像在初乳素治疗的情况下一样。对抗原反应能力的丧失可能代表导致免疫耐受的现象。