C3在迟发型超敏反应中的作用

摘要/Abstract

摘要： 目的探讨补体成分3(C3)在迟发型超敏反应(DTH)中的作用。方法用卵白蛋白(OVA)诱导C3基因敲除(C3^-/-)和野生型(C3^+/+)小鼠足垫部位的DTH,测量足垫厚度的变化,并对反应部位组织进行HE和免疫组化染色检测。分离小鼠脾脏T淋巴细胞,用巨噬细胞作为抗原提呈细胞,在体外分别用丝裂原和特异性抗原刺激,用³H-TdR掺入法评价T淋巴细胞的增殖活性。结果 OVA诱导足垫DTH后,C3^-/-小鼠足垫厚度和局部浸润单个核细胞的数量都显著低于C3^+/+小鼠的,其中浸润的单个核细胞主要为CD4⁺ T淋巴细胞。2种小鼠的T淋巴细胞对丝裂原刺激的反应相似,而已致敏C3^-/-小鼠脾脏T细胞对特异性抗原再次刺激后的增殖反应显著低于C3^+/+小鼠。结论 C3缺陷明显影响DTH应答,提示C3在DTH中起了重要作用。

Abstract: Objective To explore the role of complement C3 in delayed-type hypersensitivity (DTH). Methods After inducing DTH reaction in the footpads of C3 knockout(C3^-/-)and wild-type (C3^+/+) mice with ovalbumin (OVA), the thickness of the footpad was measured and HE and immunohistochemical staining preformed to identify the number and types of the infiltrating mononuclear cells in the footpad tissues. T lymphocytes were separated from the spleens of the mice and incubated in 96-well plates with serial dilutions of OVA or mitogens in the presence of mitomycin C-treated macrophages, and the proliferation of the T cells was assessed by ³H-TdR incorporation assay. Results The footpad thickness of DTH-C3^-/- mice was significantly smaller than that of DTH-C3^+/+ mice. The number of the infiltrating mononuclear cells in the footpad tissue of C3^-/- mice was obviously decreased in comparison with that of C3^+/+ mice, and the cells were characterized mainly as CD4⁺ T lymphocytes. No significant difference in the proliferation of mitogen-stimulated splenic T cells was noted between C3^-/- and C3^+/+ mice, but after stimulation with the specific antigen OVA, significant reduction in the proliferation of splenic T cells from C3^-/- mice was observed as compared with the T cell proliferation in C3^+/+ mice. Conclusion C3 defect results in impaired DTH responses in mice, which indicates the important role of C3 in DTH reaction.

中图分类号:

裘毅刚, 陈月, 张丽芸, 陈政良. C3在迟发型超敏反应中的作用[J]. 南方医科大学学报, 2005, 25(11): 1413-1417.

QIU Yi-gang, CHEN Yue, ZHANG Li-yun, CHEN Zheng-liang. Role of complement C3 in delayed-type hypersensitivity[J]. Journal of Southern Medical University, 2005, 25(11): 1413-1417.

参考文献

[1] Sahu A, Lambris JD. Structure and biology of complement protein C3, a connecting link between innate and acquired immunity[J].Immunol Rev, 2001, 180: 35-48.
[2] Fearon DT, Carroll MC. Regulation of B lymphocyte responses to foreign and self-antigens by the CD19/CD21 complex[J]. Annu Rev Immunol, 2000, 18: 393-422.
[3] Kopf M, Abel B, Gallimore A, et al. Complement component C3promotes T-cell priming and lung migration to control acute influenza virus infection[J]. Nat Med, 2002, 8(4): 373-8.
[4] Pratt JR., Basheer SA, Sacks SH. Local synthesis of complement component C3 regulates acute renal transplant rejection[J]. Nat Med,2002, 8(6): 82-7.
[5] Suresh M, Molina H, Salvato MS, et al. Complement component 3is required for optimal expansion of CD8 T cells during a systemic viral infection[J]. J Immunol, 2003, 170(2): 788-94.
[6] Kerekes K, Cooper PD, Prechl J, et al. Adjuvant effect of gamma-insulin is mediated by C3 fragments deposited on antigen presenting cells[J]. J Leukoc Biol, 2001, 69(1): 69-74.
[7] ChristofW, Hansch GM. The complement receptor 3, CR3 (CD11b/CD18), on T lymphocytes: activation-dependent up-regulation and regulatory function[J]. Eur J Immunol, 2001, 31(4): 1173-80.
[8] Richard GT, Jacques MC. A simple and effective method to assess murine delayed type hypersensitivity to proteins[J]. J Immunol Method, 1981, 45(4): 65-78.
[9] Sohn JH, Bora PS, Suk HJ, et al. Tolerance is dependent on complement C3 fragment iC3b binding to antigen-presenting cells[J]. Nat Med, 2003, 9(2): 206-12.
[10] Hugli TE, Muller-Eberhard HJ. Anaphylatoxins: C3a and C5a[J].Adv Immunol, 1978, 26: 1-53.
[11] Hebert MJ, Takano T, Papayianni A, et al. Acute nephrotoxic serum nephritis in complement knockout mice: relative roles of the classical and alternate pathways in neutrophil recruitment and proteinuria[J]. Nephrol Dial Transplant, 1998, 13(11): 2799-803.
[12] Kaya Z, Afanasyeva M, Wang Y, et al. Contribution of the innate immune system to autoimmune myocarditis: a role for complement[J]. Nat Immunol, 2001, 2(8): 739-45.
[13] Nataf, S, Carroll SL, Wetsel RA, et al. Attenuation of experimental autoimmune demyelination in complement-deficient mice[J]. J Immunol, 2000, 165(10): 5867-73.
[14] Kerekes K, Prechl J, Bajtay Z, et al. A further link between innate and adaptive immunity: C3 deposition on antigen-presenting cells enhances the proliferation of antigen-specific T cells[J]. Int Immunol, 1998, 10(12): 1923-30.
[15] Fischer MB, Ma M, Goerg S, et al. Regulation of the B cell response to T-dependent antigens by classical pathway complement[J]. J Immunol, 1996, 157(2): 549-56.
[16] Erdei A, Spaeth E, Alsenz J, et al. Role of C3b receptors in the enhancement of interleukin-2-dependent T-cell proliferation[J]. Mol Immunol, 1984, 21(12): 1215-21.