Gorczynski Reginald, Hoffmann Geoffrey
University of Toronto, Toronto, ON, Canada.
UBC, Vancouver, BC, Canada.
Interact J Med Res. 2017 Jul 5;6(2):e8. doi: 10.2196/ijmr.7612.
The symmetrical immune network theory, developed in 1975, is based on the existence of specific T cell factors and hypothesizes that normal IgG immune responses comprise the production of 2 kinds of antibodies, namely antigen-specific antibodies and anti-idiotypic antibodies.
The aim of this study was to confirm the existence of specific T cells factors and to show that immunization of C3H mice with BL/6 skin or using nominal antigen for immunization (Tetanus Toxoid) induced production of antigen-specific (anti-BL/6 or antitetanus) antibodies plus anti-idiotypic antibodies (C3H anti-anti-C3H). Subsequently, we investigated the role of combinations of antigen-specific and anti-idiotype antibodies in a variety of animal models of clinical diseases.
Antigen-specific antibodies were produced by conventional immunization of mice (eg, with tetanus toxoid or by skin allografting). Subsequent anti-idiotypic antibodies were derived by exhaustive absorption of antigen-specific antibody, with confirmation of anti-idiotypic specificity by binding to relevant target antigen-specific antibodies in an enzyme-linked immunosorbent assay (ELISA). Antigen-specific plus anti-idiotypic antibodies were then used to modulate skin allograft survival, dextran sulfate sodium (DSS)-induced colitis, ovalbumin (OVA)-induced IgE production, and breast cancer growth in mice.
Infusions of anti-BL/6 antibodies together with BL/6 anti-anti-BL/6 antibodies specifically suppressed (>85%) an immune response to BL/6 lymphocytes in C3H mice. The two kinds of antibodies with complementary specificity are hypothesized to stimulate 2 populations of T lymphocytes. Coselection of these 2 populations leads to a new stable steady state of the system with diminished reactivity to BL/6 tissue. A combination of anti-C3H and C3H anti‑anti-C3H IgG antibodies down-regulated inflammation in a mouse model of inflammatory bowel disease (>75%) and attenuated anti-IgE production and sensitization to produce IL4 cytokines (>70%) in an OVA-allergy model. Combination of C3H anti‑BL/6 and BL/6 anti-anti-BL/6 antibodies decreased tumor growth and metastases (>705) in an EMT6 transplantable breast cancer model.
Use of a combination of antigen-specific and anti-idiotypic antibodies has potential as a new class of vaccines.
1975年提出的对称免疫网络理论基于特异性T细胞因子的存在，并假设正常的IgG免疫反应包括两种抗体的产生，即抗原特异性抗体和抗独特型抗体。
本研究旨在证实特异性T细胞因子的存在，并表明用BL/6皮肤免疫C3H小鼠或使用名义抗原（破伤风类毒素）进行免疫可诱导产生抗原特异性（抗BL/6或抗破伤风）抗体以及抗独特型抗体（C3H抗抗C3H）。随后，我们在多种临床疾病动物模型中研究了抗原特异性抗体和抗独特型抗体组合的作用。
通过常规免疫小鼠（如用破伤风类毒素或皮肤同种异体移植）产生抗原特异性抗体。随后通过彻底吸收抗原特异性抗体获得抗独特型抗体，并通过酶联免疫吸附测定（ELISA）中与相关靶抗原特异性抗体结合来确认抗独特型特异性。然后使用抗原特异性抗体加抗独特型抗体来调节小鼠皮肤同种异体移植存活、硫酸葡聚糖钠（DSS）诱导的结肠炎、卵清蛋白（OVA）诱导的IgE产生以及乳腺癌生长。
将抗BL/6抗体与BL/6抗抗BL/6抗体一起输注可特异性抑制（>85%）C3H小鼠对BL/6淋巴细胞的免疫反应。假设具有互补特异性的这两种抗体可刺激两群T淋巴细胞。这两群细胞的共同选择导致系统出现新的稳定稳态，对BL/6组织的反应性降低。抗C3H和C3H抗抗C3H IgG抗体的组合在炎症性肠病小鼠模型中下调炎症（>75%），并在OVA过敏模型中减弱抗IgE产生和产生IL4细胞因子的致敏作用（>70%）。C3H抗BL/6和BL/6抗抗BL/6抗体的组合在EMT6可移植乳腺癌模型中减少肿瘤生长和转移（>70%）。
使用抗原特异性抗体和抗独特型抗体的组合作为新型疫苗具有潜力。
