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首页> 外文期刊>The journal of immunology >Rapid and Long-Term Disappearance of CD4+ T Lymphocyte Responses Specific for Anaplasma Marginale Major Surface Protein-2 (MSP2) in MSP2 Vaccinates following Challenge with Live A. marginale
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Rapid and Long-Term Disappearance of CD4+ T Lymphocyte Responses Specific for Anaplasma Marginale Major Surface Protein-2 (MSP2) in MSP2 Vaccinates following Challenge with Live A. marginale

机译：快速和长期消失的MS4接种特异性针对无缘无缘质膜主要表面蛋白2（MSP2）的CD4 + T淋巴细胞反应后，挑战了活的A.marginale

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In humans and ruminants infected with Anaplasma , the major surface protein 2 (MSP2) is immunodominant. Numerous CD4+ T cell epitopes in the hypervariable and conserved regions of MSP2 contribute to this immunodominance. Antigenic variation in MSP2 occurs throughout acute and persistent infection, and sequentially emerging variants are thought to be controlled by variant-specific Ab. This study tested the hypothesis that challenge of cattle with Anaplasma marginale expressing MSP2 variants to which the animals had been immunized, would stimulate variant epitope-specific recall CD4+ T cell and IgG responses and organism clearance. MSP2-specific T lymphocyte responses, determined by IFN-γ ELISPOT and proliferation assays, were strong before and for 3 wk postchallenge. Surprisingly, these responses became undetectable by the peak of rickettsemia, composed predominantly of organisms expressing the same MSP2 variants used for immunization. Immune responsiveness remained insignificant during subsequent persistent A. marginale infection up to 1 year. The suppressed response was specific for A. marginale , as responses to Clostridium vaccine Ag were consistently observed. CD4+CD25+ T cells and cytokines IL-10 and TGF-β1 did not increase after challenge. Furthermore, a suppressive effect of nonresponding cells was not observed. Lymphocyte proliferation and viability were lost in vitro in the presence of physiologically relevant numbers of A. marginale organisms. These results suggest that loss of memory T cell responses following A. marginale infection is due to a mechanism other than induction of T regulatory cells, such as peripheral deletion of MSP2-specific T cells.
机译：在人和反刍动物感染无浆膜中，主要表面蛋白2（MSP2）具有免疫优势。 MSP2的高变和保守区域中的许多CD4 + T细胞表位有助于这种免疫优势。 MSP2的抗原变异发生在整个急性和持续感染中，因此顺序出现的变异被认为是由变异特异性抗体控制的。这项研究检验了以下假设：用已免疫动物的表达MSP2变种的边缘无浆膜质子对牛的攻击将刺激变体表位特异性召回CD4 + T细胞和IgG反应以及生物清除。攻击前和攻击后3周，通过IFN-γELISPOT和增殖分析确定的MSP2特异性T淋巴细胞反应强烈。出乎意料的是，立克次体血症的峰值无法检测到这些反应，而立克次体血症主要由表达用于免疫的相同MSP2变体的生物组成。在随后的持续性边缘margin曲霉感染长达1年的期间，免疫反应仍然不明显。由于一直观察到对梭状芽胞杆菌疫苗Ag的应答，所以抑制的应答是对边缘margin曲霉特异的。攻击后，CD4 + CD25 + T细胞和细胞因子IL-10和TGF-β1没有增加。此外，未观察到无应答细胞的抑制作用。在生理上相关数量的边缘拟南芥生物的存在下，体外淋巴细胞的增殖和活力丧失。这些结果表明，边缘拟南芥感染后记忆T细胞应答的丧失是由于除了诱导T调节细胞以外的其他机制引起的，例如MSP2特异性T细胞的外周缺失。

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