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首页> 外文期刊>Infection and immunity >Frequencies of Region of Difference 1 Antigen-Specific but Not Purified Protein Derivative-Specific Gamma Interferon-Secreting T Cells Correlate with the Presence of Tuberculosis Disease but Do Not Distinguish Recent from Remote Latent Infections
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Frequencies of Region of Difference 1 Antigen-Specific but Not Purified Protein Derivative-Specific Gamma Interferon-Secreting T Cells Correlate with the Presence of Tuberculosis Disease but Do Not Distinguish Recent from Remote Latent Infections

机译：差异1抗原特异性但未纯化的蛋白质衍生物特异性γ干扰素分泌T细胞区域的频率与结核病的存在相关，但不能与近期的潜在潜伏感染区分开

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The majority of individuals infected with Mycobacterium tuberculosis achieve lifelong immune containment of the bacillus. What constitutes this effective host immune response is poorly understood. We compared the frequencies of gamma interferon (IFN-γ)-secreting T cells specific for five region of difference 1 (RD1)-encoded antigens and one DosR-encoded antigen in 205 individuals either with active disease (n = 167), whose immune responses had failed to contain the bacillus, or with remotely acquired latent infection (n = 38), who had successfully achieved immune control, and a further 149 individuals with recently acquired asymptomatic infection. When subjects with an IFN-γ enzyme-linked immunospot (ELISpot) assay response to one or more RD1-encoded antigens were analyzed, T cells from subjects with active disease recognized more pools of peptides from these antigens than T cells from subjects with nonrecent latent infection (P = 0.002). The T-cell frequencies for peptide pools were greater for subjects with active infection than for subjects with nonrecent latent infection for summed RD1 peptide pools (P ≤ 0.006) and culture filtrate protein 10 (CFP-10) antigen (P = 0.029). Individuals with recently acquired (<6 months) versus remotely acquired (>6 months) latent infection did not differ in numbers of peptide pools recognized, proportions recognizing any individual antigen or peptide pool, or antigen-specific T-cell frequencies (P ≥ 0.11). The hierarchy of immunodominance for different antigens was purified protein derivative (PPD) > CFP-10 > early secretory antigenic target 6 > Rv3879c > Rv3878 > Rv3873 > Acr1, and the hierarchies were very similar for active and remotely acquired latent infections. Responses to the DosR antigen α-crystallin were not associated with latency (P = 0.373). In contrast to the RD1-specific responses, the responses to PPD were not associated with clinical status (P > 0.17) but were strongly associated with positive tuberculin skin test results (≥15-mm induration; P ≤ 0.01). Our results suggest that RD1-specific IFN-γ-secreting T-cell frequencies correlate with the presence of disease rather than with protective immunity in M. tuberculosis-infected individuals and do not distinguish recently acquired asymptomatic infection from remotely acquired latent infection.
机译：感染结核分枝杆菌的大多数人都能终生免疫细菌。人们对有效的宿主免疫反应的构成了解甚少。我们比较了205例患有活动性疾病（ n ）的个体对5个差异1（RD1）编码抗原和一种DosR编码抗原特异性分泌γ干扰素（IFN-γ）的T细胞的频率。 > = 167），其免疫反应未能包含芽孢杆菌，或具有成功获得免疫控制的远程获得性潜伏感染（ n = 38），还有149个人最近获得了无症状感染。当分析接受IFN-γ酶联免疫斑点（ELISpot）分析的受试者对一种或多种RD1编码抗原的反应时，患有活动性疾病的受试者的T细胞比来自非潜伏性受试者的T细胞识别出更多的来自这些抗原的肽库感染（ P = 0.002）。对于总的RD1肽库（ P ≤0.006）和培养物滤液蛋白10（CFP-10）抗原，活动性感染受试者的肽库T细胞频率高于非近期潜伏性感染受试者。 （ P = 0.029）。近期获得感染（<6个月）与远程获得感染（> 6个月）的个体在识别的肽库数量，识别任何单个抗原或肽库的比例或抗原特异性T细胞频率方面没有差异（ P ≥0.11）。不同抗原的免疫优势层次为纯化蛋白衍生物（PPD）> CFP-10>早期分泌性抗原靶标6> Rv3879c> Rv3878> Rv3873> Acr1，并且对于活动性和远程获得性潜伏感染，其层次非常相似。对DosR抗原α-晶状体蛋白的反应与潜伏期无关（ P = 0.373）。与RD1特异性反应相反，对PPD的反应与临床状态无关（ P P ≤0.01）。我们的结果表明，分泌RD1的特定IFN-γ的T细胞频率与疾病的存在相关，而不与 M中的保护性免疫相关。感染结核病的个体，不能将近期获得的无症状感染与远程获得性潜伏感染区分开来。

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