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慢性实验性恰加斯病:在无外源性刺激情况下体外功能性同基因T-B细胞协作

Chronic experimental Chagas' disease: functional syngeneic T-B-cell cooperation in vitro in the absence of an exogenous stimulus.

作者信息

Freire-de-Lima C, Peçanha L M, Dos Reis G A

机构信息

Department of Immunology, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Brazil.

出版信息

Infect Immun. 1996 Jul;64(7):2861-6. doi: 10.1128/iai.64.7.2861-2866.1996.

Abstract

We have investigated CD4+ T-cell autoreactivity to normal syngeneic B cells in vitro in chronic experimental Chagas' disease. Resting B cells induced an intense proliferative response and lymphokine secretion by splenic CD4+ T cells from Trypanosoma cruzi-infected (8 months or more of infection) donors, compared to much lower responses by uninfected controls. On the other hand, lipopolysaccharide-activated B cells induced syngeneic CD4+ T-cell activation in both control and infected groups. The observed syngeneic T-B-cell cooperation was bidirectional. In the absence of any exogenous stimulus, CD4+ T cells from T. cruzi-infected animals induced much higher production of all tested immunoglobulin (Ig) isotypes (IgM, IgG1, IgG2a, IgG2b, IgG3) by syngeneic B cells, compared to T cells from uninfected donors. When lipopolysaccharide-treated B cells were used, CD4+ T cells from either control or infected donors enhanced IgG1 and IgG3 production, but only CD4+ T cells of infected origin induced IgG2a production in this system without addition of exogenous gamma interferon. Enhanced T-cell proliferation and Ig production were also observed with highly purified CD4+ T cells and in serum-free medium. Both proliferation and Ig production could be blocked with anti-major histocompatibility complex class II monoclonal antibodies. Enhanced reactivity and help for Ig production were seen only in response to syngeneic BALB B cells and not in response to allogeneic B10 B cells. These results indicate that chronic infection with T. cruzi results in increased CD4+ T-cell reactivity towards syngeneic B cells, which leads to spontaneous Ig production. These autoreactive T cells might play a role in polyclonal autoantibody production in chronic Chagas' disease.

摘要

我们在慢性实验性恰加斯病中,对体外CD4 + T细胞针对同基因正常B细胞的自身反应性进行了研究。与未感染的对照组相比,来自感染克氏锥虫(感染8个月或更长时间)供体的脾脏CD4 + T细胞,对静止B细胞诱导出强烈的增殖反应和淋巴因子分泌。另一方面,脂多糖激活的B细胞在对照组和感染组中均诱导同基因CD4 + T细胞活化。观察到的同基因T - B细胞协作是双向的。在没有任何外源性刺激的情况下,与未感染供体的T细胞相比,来自克氏锥虫感染动物的CD4 + T细胞诱导同基因B细胞产生所有测试免疫球蛋白(Ig)同种型(IgM、IgG1、IgG2a、IgG2b、IgG3)的产量要高得多。当使用脂多糖处理的B细胞时,来自对照组或感染供体的CD4 + T细胞增强了IgG1和IgG3的产生,但只有感染来源的CD4 + T细胞在不添加外源性γ干扰素的情况下,在该系统中诱导IgG2a的产生。在高度纯化的CD4 + T细胞和无血清培养基中也观察到T细胞增殖和Ig产生增强。增殖和Ig产生均可被抗主要组织相容性复合体II类单克隆抗体阻断。增强的反应性和对Ig产生的辅助作用仅在对同基因BALB B细胞的反应中可见,而对异基因B10 B细胞无反应。这些结果表明,克氏锥虫的慢性感染导致CD4 + T细胞对同基因B细胞的反应性增加,从而导致自发的Ig产生。这些自身反应性T细胞可能在慢性恰加斯病的多克隆自身抗体产生中起作用。

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