Interleukin 2-diphtheria toxin fusion protein can abolish cell-mediated immunity in vivo.
Interleukin 2-diphtheria toxin fusion protein can abolish cell-mediated immunity in vivo.
复制标题
白介素2-白喉毒素融合蛋白可以消除体内细胞介导的免疫。
DOI：
10.1073/pnas.85.11.3980
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发表时间：
1988
影响因子：
11.1
通讯作者：
Strom,TB
中科院分区：
文献类型：
--
作者：
Kelley,VE;Bacha,P;Pankewycz,O;Nichols,JC;Murphy,JR;Strom,TB
De novo expression of the interleukin 2 receptor (IL-2R) is a critical and pivotal event in initiation of an immune response. Targeting the low-affinity IL-2-binding p55 subunit of the high-affinity IL-2R with the rat anti-mouse IgM monoclonal antibody M7/20 suppresses a variety of T-cell-mediated reactions, including transplant rejection, autoimmunity, and delayed-type hypersensitivity (DTH). A hybrid IL-2-toxin gene was constructed from the diphtheria toxin gene by replacing the DNA encoding the diphtheria toxin receptor-binding domain with the DNA encoding the receptor-binding domain of IL-2, and the fusion protein encoded by the hybrid gene was expressed in Escherichia coli [Williams, D.P., Parker, K., Bacha, P., Bishai, W., Borowski, M., Genbauffe, F., Strom, T.B. & Murphy, J.R. (1987) Protein Eng. 1, 493-498]. We examined the action of the chimeric IL-2-toxin fusion protein on an in vivo T-cell mediated response, DTH. The IL-2-toxin fusion protein was found to be a potent immunosuppressive agent. Treatment of mice with the IL-2-toxin blocks DTH and prevents expansion of IL-2R+ T cells. Indeed, IL-2-toxin treatment targets IL-2R+ T cells in vivo and is shown to selectively eliminate their appearance in draining lymph nodes. DTH suppression was observed even in mice possessing high titers of antibodies to diphtheria toxoid.
