Administration of monoclonal anti-T cell antibodies retards murine lupus in BXSB mice.
Administration of monoclonal anti-T cell antibodies retards murine lupus in BXSB mice.
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DOI：
10.4049/jimmunol.136.12.4554
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发表时间：
1986-06
影响因子：
4.4
通讯作者：
D. Wofsy
中科院分区：
文献类型：
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作者：
D. Wofsy
BXSB小鼠中的鼠狼疮与B细胞过度活跃、单核细胞增殖和受损的T细胞功能有关。然而，这些异常的意义，以及它们之间的关系，尚未明确建立。为了研究T细胞在BXSB小鼠自身免疫性疾病发病机制中的作用，我们通过使用大鼠IgG 2b单克隆抗体（MAb）对Thy-1.2（在所有T细胞上）或L3 T4（在“辅助/诱导”T细胞上）耗尽BXSB雄性的特异性T细胞亚群。单次注射抗Thy-1.2（6 mg i. v.）在3个月大时，在6个月内循环T细胞持续减少40 - 50%。治疗预防单核细胞增多症，降低抗DNA抗体浓度，延缓肾脏疾病，但不能延长生命。重复注射大鼠抗Thy-1.2单克隆抗体可导致BXSB小鼠产生对大鼠免疫球蛋白（IG）的宿主免疫应答，从而导致过敏反应。相反，大鼠抗L3 T4单克隆抗体对大鼠IG的免疫应答很少或没有刺激。因此，我们能够每周用抗L3 T4（2 mg i. p.）从3岁到12个月通过荧光分析，处理将循环L3 T4+细胞减少到检测水平以下。它还显著降低单核细胞增多症、抗DNA抗体产生、肾脏疾病和死亡率。这些发现证实了BXSB小鼠中单核细胞增多和自身免疫是由T细胞促进的。他们扩展了我们先前的观察，即抗L3 T4单克隆抗体延缓NZB/NZW F1小鼠的自身免疫。我们的发现，单克隆抗体治疗L3 T4是有效的两个品系的狼疮倾向的小鼠表明，单克隆抗体治疗Leu-3/T4，人类同系物L3 T4，可能是有效的人与系统性红斑狼疮。
Murine lupus in BXSB mice is associated with B cell hyperactivity, monocyte proliferation, and impaired T cell function. However, the significance of these abnormalities, and the relationship among them, has not been clearly established. To examine the role of T cells in the pathogenesis of autoimmune disease in BXSB mice, we depleted specific T cell subsets from BXSB males by using rat IgG2b monoclonal antibodies (MAb) to either Thy-1.2 (on all T cells) or L3T4 (on "helper/inducer" T cells). A single injection of anti-Thy-1.2 (6 mg i.v.) at age 3 mo produced a sustained 40 to 50% reduction in circulating T cells for 6 mo. Treatment prevented monocytosis, reduced anti-DNA antibody concentration, and retarded renal disease, but it did not prolong life. Repeated injections of rat MAb to Thy-1.2 were precluded by the development of a host immune response to rat immunoglobulin (Ig) that can cause anaphylaxis in BXSB mice. In contrast, rat MAb to L3T4 stimulated little or no immune response to rat Ig. We therefore were able to treat BXSB mice weekly with anti-L3T4 (2 mg i.p.) from age 3 to 12 mo. Treatment reduced circulating L3T4+ cells beneath the level of detection by fluorescence analysis. It also significantly reduced monocytosis, anti-DNA antibody production, renal disease, and mortality. These findings establish that monocytosis and autoimmunity in BXSB mice are promoted by T cells. They extend our previous observation that MAb to L3T4 retard autoimmunity in NZB/NZW F1 mice. Our finding that treatment with MAb to L3T4 is effective in two strains of lupus-prone mice suggests that treatment with MAb to Leu-3/T4, the human homologue for L3T4, may be effective in people with systemic lupus erythematosus.