Heo Y, Lee W T, Lawrence D A
Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA.
Cell Immunol. 1997 Aug 1;179(2):185-95. doi: 10.1006/cimm.1997.1160.
An oligoclonal utilization of Vbetas has been reported for pathogenesis of several autoimmune diseases, anti-tumorigenic activity, and superantigen-regulation of thymic T cell development. Altered ratios of Th1 and Th2 cells also are observed in immunodysregulations, leading to impaired cell-mediated immunity with an increased incidence of infectious disease or cancer and/or aberrant immunity that could culminate with an autoimmune disease. Lead (Pb) and mercury (Hg) are known pollutants with immunodisrupting activities; Hg is known to cause autoimmune glomerulonephritis. Both metals are known to suppress host resistance to pathogens. To further evaluate the manner by which these metals cause in vivo immunomodulation, their in vivo effects on Vbeta expression were evaluated along with the Th1 and Th2 frequency. Exposure of BALB/c mice to PbCl2 or HgCl2 induced an oligoclonal response with increases of Vbeta 5+, Vbeta 7+, and Vbeta 13+ CD4+ splenic, but not thymic, T cells. A significantly skewed frequency of Pb-induced splenic Th2 cells expressing Vbeta 7 or Vbeta 13 over Th1 cells was determined by limiting dilution analysis, but this Th2 predominance was not observed with CD4+ T cells expressing Vbeta 8. DO11.10 transgenic mouse exposed to Pb and antigen also demonstrated a skewed type-2 response evidenced by significantly increased IgE levels, lowered IFN-gamma levels, and increased IgG1 and lowered IgG2a anti-OVA levels. Even in the absence of specific T cell responses to a Pb-induced antigen, due to the restricted T cell specificity in the transgenic mouse model, Pb still was able to skew the response toward type-2 reactivity. However, this skewing occurred only in the presence of antigen. Therefore, the Pb-induced oligoclonal T cell response in BALB/c mice which must be initiated by self-antigens and was predominately type-2 may be responsible for autoantibody production and the detrimental health effects associated with Pb exposure.
据报道，Vβ的寡克隆利用与多种自身免疫性疾病的发病机制、抗肿瘤活性以及胸腺T细胞发育的超抗原调节有关。在免疫调节异常中也观察到Th1和Th2细胞比例的改变，导致细胞介导的免疫受损，传染病或癌症的发病率增加，和/或异常免疫，最终可能导致自身免疫性疾病。铅（Pb）和汞（Hg）是已知具有免疫破坏活性的污染物；已知Hg可引起自身免疫性肾小球肾炎。这两种金属都已知会抑制宿主对病原体的抵抗力。为了进一步评估这些金属在体内引起免疫调节的方式，评估了它们对Vβ表达的体内影响以及Th1和Th2频率。将BALB/c小鼠暴露于PbCl2或HgCl2会诱导寡克隆反应，脾脏而非胸腺的CD4+T细胞中Vβ5+、Vβ7+和Vβ13+增加。通过有限稀释分析确定，Pb诱导的表达Vβ7或Vβ13的脾脏Th2细胞频率相对于Th1细胞明显偏斜，但在表达Vβ8的CD4+T细胞中未观察到这种Th2优势。暴露于Pb和抗原的DO11.10转基因小鼠也表现出偏斜的2型反应，表现为IgE水平显著升高、IFN-γ水平降低、IgG1升高和抗OVA的IgG2a水平降低。即使在转基因小鼠模型中由于T细胞特异性受限而不存在对Pb诱导抗原的特异性T细胞反应时，Pb仍然能够使反应偏向2型反应性。然而，这种偏斜仅在有抗原存在时发生。因此，BALB/c小鼠中由自身抗原引发且主要为2型的Pb诱导的寡克隆T细胞反应可能是自身抗体产生以及与Pb暴露相关的有害健康影响的原因。
