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Resolution of chlamydial genital infection with antigen-specific T-lymphocyte lines.

机译:用抗原特异性T淋巴细胞株解决衣原体生殖器感染。

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To determine cell-mediated immune mechanisms involved in the resolution of chlamydial genital infection of mice, we utilized an established murine model in which it has been demonstrated that resolution of infection occurs independently of the antibody response. Splenic T lymphocytes were obtained from mice that had previously been immunized with viable elementary bodies of the mouse pneumonitis agent (MoPn), a Chlamydia trachomatis biovar. Antigen-reactive T lymphocytes were maintained and expanded in vitro by frequent restimulation with UV light-inactivated MoPn in the presence of antigen-presenting cells and recombinant interleukin-2 (rIL-2). Flow cytometry indicated that this cell line was at least 92% positive for the pan-specific T-cell marker Thy1.2. Stimulation of the cells in the presence of syngeneic antigen-presenting cells plus MoPn antigen and in the absence of exogenous IL-2 induced the cells to produce IL-2 activity in culture supernatants. Following adoptive transfer, this T-lymphocyte line was effective in inducing resolution of an ongoing MoPn genital infection in congenitally athymic nude mice which otherwise maintain chronic unresolved infections. The line was less efficient in resolving the infection after longer periods in culture. An additional T-lymphocyte line was derived from the spleens of athymic mice that had received the first line and had resolved the infection. These T cells were also capable of inducing resolution of the infection. Lastly, this cell line was treated with specific antibody and complement to delete either CD4+ or CD8+ T lymphocytes in an attempt to enrich for T-cell subpopulations prior to transfer into infected athymic mice. The anti-CD4-treated line was essentially depleted of CD4 cells, while the anti-CD8-treated line was only partially enriched for CD4 cells, with a large proportion of CD8 cells still present. Nude mice that received either of the treated T-cell lines or the parental cell line were capable of resolving the infection, although the line with increased numbers of CD4 cells was more efficient than either the parental line or the CD8 line.
机译:为了确定参与小鼠衣原体生殖器感染消退的细胞介导的免疫机制,我们利用已建立的鼠模型,其中已经证明感染的消退独立于抗体应答而发生。脾脏T淋巴细胞是从小鼠中获得的,该小鼠先前已经用小鼠肺炎沙眼衣原体生物变种(MoPn)的存活基本体进行了免疫。在抗原呈递细胞和重组白介素2(rIL-2)存在下,通过用紫外线灭活的MoPn频繁地再刺激,可以在体外维持和扩增抗原反应性T淋巴细胞。流式细胞术表明,该细胞系对泛特异性T细胞标记Thy1.2至少具有92%阳性。在存在同质抗原呈递细胞加MoPn抗原的情况下以及在不存在外源IL-2的情况下刺激细胞诱导细胞在培养上清液中产生IL-2活性。过继转移后,该T淋巴细胞系可有效诱导先天性无胸腺裸鼠中正在进行的MoPn生殖器感染的消退,否则该裸鼠会保持慢性未解决的感染。经过较长时间的培养后,该品系在解决感染方面效率较低。另一只T淋巴细胞系来自无胸腺小鼠的脾脏,这些小鼠已经接受了第一系并已解决了感染。这些T细胞也能够诱导感染的消退。最后,用特异性抗体和补体处理该细胞系以删除CD4 +或CD8 + T淋巴细胞,以尝试在转移到感染的无胸腺小鼠之前富集T细胞亚群。抗-CD4处理的细胞系基本上耗尽了CD4细胞,而抗-CD8处理的细胞系仅部分地富集了CD4细胞,但仍存在很大比例的CD8细胞。接受治疗的T细胞系或亲本细胞系的裸鼠均能够解决感染,尽管CD4细胞数量增加的系比亲本系或CD8系更有效。

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