地塞米松对儿童原发性系膜增生性肾炎外周血淋巴细胞CTLA-4表达和凋亡的影响

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摘要目的：原发性系膜增生性肾炎(MsPGN)的发病机制和糖皮质激素(GC)耐药机制虽然部分已明确，但其确切机制仍未阐明。细胞毒性T淋巴细胞相关抗原(CTLA-4)是T细胞活化的重要抑制性分子。本研究探讨MsPGN患儿外周血淋巴细胞CTLA-4表达和淋巴细胞凋亡及地塞米松(Dex)对其影响。方法：分别采用直接免疫荧光、流式细胞仪及Annexin V-FITC/PI双染流式细胞仪检测Dex处理或非Dex处理的MsPGN组和对照组体外培养外周血淋巴细胞膜CTLA-4的表达和其凋亡。结果：体外培养MsPGN组淋巴细胞CTLA-4的自然表达和Dex诱导的表达均较对照组低（P＜0.05）；MsPGN组淋巴细胞自然凋亡和Dex诱导的凋亡亦较对照组低（P＜0.05），且两者均呈正相关性（P＜0.05）。结论：CTLA-4表达异常可能参与了MsPGN的发病机制及GC耐药机制。［中国当代儿科杂志，2009，11（12）：957-960］

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	王凤英
	卢思广
	罗荣华

关键词 ：系膜增生性肾炎, CTLA-4, 地塞米松, 凋亡, 儿童

Abstract：OBJECTIVE: The pathogenesis of mesangial proliferative glomerulonephritis (MsPGN) and mechanisms of glucocorticoid (GC) resistance have not been fully identified. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is an important inhibitor of T-lymphocyte activation. The objective of the study is to investigate the CTLA-4 expression and apoptosis in lymphocytes of children with MsPGN and the effects of dexamethasone (Dex) on the CTLA-4 expression and apoptosis. METHODS: Blood samples were collected from 36 children with MsPGN and 30 healthy children. CTLA-4 expression in in vitro cultured lymphocytes with or without Dex treatment was measured by flow cytometry following direct immune fluorescene. The rate of apoptosis in the lymphocytes was evaluated by annexin V-FITC and propidium iodide staining. RESULTS: The CTLA-4 expression and apoptosis in lymphocytes from children with MsPGN were significantly lower than those in the healthy control children in the absence or presence of Dex treatment (P＜0.05). There was a positive correlation between CTLA-4 expression and apoptosis in lymphocytes (P＜0.05). CONCLUSIONS: Abnormal CTLA-4 expression may participate in the pathogenesis of MsPGN and be one of mechanisms of GC resistance.［Chin J Contemp Pediatr, 2009, 11 (12):957-960］

Key words： Mesangial proliferative glomerulonephritis CTLA-4 Dexamethasone Apoptosis Child

PACS:

R692.3

引用本文:

王凤英,卢思广,罗荣华. 地塞米松对儿童原发性系膜增生性肾炎外周血淋巴细胞CTLA-4表达和凋亡的影响[J]. 中国当代儿科杂志, 2009, 11(12): 957-960.

WANG Feng-Ying,LU Si-Guang,LUO Rong-Hua. Effects of dexamethasone on CTLA-4 expression and apoptosis in lymphocytes obtained from children with mesangial proliferative nephritis[J]. CJCP, 2009, 11(12): 957-960.

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http://www.zgddek.com/CN/ 或 http://www.zgddek.com/CN/Y2009/V11/I12/957

	［1］Kato T, Nariuchi H. Polarization of naive CD4+ T cells toward the Th1 subset by CTLA-4 costimulation［J］. J Immunol, 2000, 164(7):3554-3562.
	［2］Frauwirth KA, Thompson CB. Activation and inhibition of lymphocytes by costimulation［J］. J Clin Invest, 2002, 109(3):295-299.
	［3］Parrv RV, Chemnitz JM, Frauwirth KA, Lanfranco AR, Braunstein I, Kobavashi SV, et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms［J］. Mol Cell Biol, 2005, 25(21):9543-9553.
	［4］Henson SM, Macaulav R, Kiani-Alikhan S, Akbar AN. The use of the inhibiotory receptors for modulating the immune responses［J］. Curr Pharm Des, 2008, 14(26):26432650.
	［5］中华医学会儿科学分会肾脏病学组.小儿肾小球疾病的临床分类、诊断及治疗［J］.中华儿科杂志, 2001, 39(12):746-749.
	［6］Xia M, Gasser J, Feige U. Dexamethasone enhances CTLA-4 expression during T cell activation［J］. Cell Mol Life Sci, 1999, 55(12):1649-1656.
	［7］Koper JW, Stolk RP, Delange P, Huizenga NA, Molijn GJ, Pols HA, et al. Lack of association between five polymorphisms in the human glucocorticoid receptor gene and glucocorticoid resistance［J］. Hum Genet, 1997, 99(5):663-668.
	［8］Linsley PS, Bradshaw J, Greene J, Peach R, Bennett KL, Mittler RS. Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement［J］. Immunity, 1996, 4(6):535-543.
	［9］Egen JG, Kuhns MS, Allison JP. CTLA-4: new insights into its biological function and use in tumor immunotherapy［J］. Nat Immunol, 2002, 3(7):611-618.
	［10］Martin M, Schneider H, Azouz A, Rudd CE. Cytotoxic T lymphocyte antigen 4 and CD28 modulate cell surface raft expression in their regulation of T cell function［J］. J Exp Med, 2001, 194(11):1675-1681.
	［11］Kubsch S, Graulich E, Knop J, Steinbrink K. Suppressor activity of anergic T cells induced by IL-10-treated human dendritic cells: association with IL-2-and CTLA-4-dependent G1 arrest of the cell cycle regulated by p27Kip1［J］. Eur J Immunol, 2003, 33(7):1988-1997.
	［12］Contardi E, Palmisano GL, Tazzari PL, Martelli AM, Falà F, Fabbi M, et al. CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction［J］. Int J Cancer, 2005, 117(4):538-550.
	［13］Laurent S, Palmisano GL, Martelli AM, Kato T, Tazzari PL, Pierri I, et al. CTLA-4 expressed by chemoresistant, as well as untreated, myeloid leukaemia cells can be targeted with ligands to induce apoptosis［J］. Br J Haematol, 2007, 136(4):597-608.
	［14］Harlin H, Hwang KW, Palucki DA, Kim O, Thompson CB, Boothbv M, et al. CTLA-4 engagement regulates NF-kappaB activation in vivo［J］. Eur J Immunol, 2002, 32(8):2095-2104.
	［15］Bour-Jordan H, Grogan JL, Tang Q, Auqer JA, Lockslev RM, Bluestone JA. CTLA-4 regulates the requirement for cytokine-induced signals in T（H）2 lineage commitment［J］. Nat Immunol, 2003, 4(2):182-188.