同型
抗体
单克隆抗体
免疫学
免疫球蛋白类转换
实验性自身免疫性脑脊髓炎
单克隆
脑脊髓炎
B细胞
生物
分子生物学
免疫系统
多发性硬化
作者
Matthew K. Waldor,Dennis J. Mitchell,Thomas J. Kipps,Leonard A. Herzenberg,Lawrence Steinman
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:1987-12-01
卷期号:139 (11): 3660-3664
被引量:27
标识
DOI:10.4049/jimmunol.139.11.3660
摘要
Experimental allergic encephalomyelitis (EAE) is an autoimmune disease mediated by CD4+ T cells. Prior studies have established that monoclonal anti-CD4 antibodies can reverse EAE. To determine whether immunoglobulin isotype plays a role in the therapy of EAE with anti-CD4 antibody, an isotype switch variant family of the mouse IgG1 anti-rat CD4 antibody W3/25 was isolated with the fluorescence-activated cell sorter. The IgG1, IgG2b, and IgG2a W3/25 isotype variants all had identical binding capacities for rat CD4+ T cells. Although all three W3/25 isotypes showed some beneficial effects in the amelioration of EAE, the IgG1 and IgG2a W3/25 antibodies were superior to the IgG2b W3/25 in the treatment of EAE. Multiparameter fluorescence-activated cell sorter analysis of T cell subpopulations from treated rats showed that none of the antibodies of the W3/25 isotype switch variant family substantially depleted CD4+ target cells in vivo. These experiments demonstrate that immunoglobulin isotype is important in the monoclonal antibody therapy of autoimmune disease. They indicate that therapy of EAE may be successful without a major depletion of CD4+ lymphocytes. Immunotherapy may be optimized by selecting an appropriate isotype of a monoclonal antibody.
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