白癜风免疫微环境对黑素细胞CXCL10表达的影响

目的:明确白癜风免疫微环境对黑素细胞CXCL10表达的影响。方法:采用qRT-PCR检测进展期白癜风患者皮损组织中的细胞因子;采用qRT-PCR及ELISA检测白癜风免疫微环境中上调的细胞因子对黑素细胞系PIG1 CXCL10表达和分泌。结果:进展期白癜风患者皮损组织中IFN-γ、TNF-α和IL-1βmRNA表达上调;三者联合刺激显著上调PIG1细胞CXCL10 mRNA的表达以及蛋白分泌,并呈现时间依赖性。结论:白癜风局部免疫微环境促进黑素细胞表达及分泌CXCL10,可能参与白癜风发病。     

白癜风患者血清亚油酸的水平及其对CD8~+T细胞的作用

目的探究白癜风患者外周血中亚油酸(linoleic acid,LA)的水平及其对外周血CD8~+T细胞的作用。方法利用超高效液相色谱-质谱非靶向代谢联用技术检测8例白癜风患者及8例健康对照者血清中代谢物LA的水平,采用流式细胞术检测5例白癜风患者及5例健康对照者外周血中CD8~+T细胞的活化及杀伤性分子表达情况,最后体外常规培养5例患者外周血CD8~+T细胞,予以LA刺激,明确LA对白癜风患者外周血CD8~+T细胞活化及杀伤分子表达的影响。结果与健康对照相比,白癜风患者血清中LA水平显著升高(P0.05),且外周血CD8~+T细胞过度活化(P0.05)并高表达毒性杀伤分子颗粒酶B(granzyme B,GzmB,P0.05)、穿孔素(perforin,PRF,P0.05);进一步体外试验发现LA显著抑制白癜风患者外周血CD8~+T细胞的活化及毒性杀伤效应分子的表达。结论进展期白癜风患者血清中LA水平上调,可抑制CD8~+T细胞活化及杀伤效应功能,帮助机体重建自身免疫紊乱后平衡状态。     

卵巢滤泡激素在干扰素γ介导的黑素细胞凋亡以及趋化因子分泌中的作用研究

【摘要】 目的 研究卵巢滤泡激素（FLCN）在干扰素γ（IFN-γ）介导的黑素细胞凋亡及趋化因子分泌中发挥的作用。方法 从正常人包皮环切组织及白癜风移植患者正常部位的吸疱表皮分离正常原代黑素细胞及白癜风原代黑素细胞。采用Western印迹检测正常原代黑素细胞、白癜风原代黑素细胞及人原代黑素细胞系PIG1细胞中FLCN蛋白的表达。以10 ng/ml IFN-γ刺激48 h的PIG1细胞为诱导组,未经处理的PIG1细胞为对照组,采用qRT-PCR检测两组细胞FLCN及自噬相关微管相关蛋白1轻链3（LC3）Ⅱ、Beclin基因mRNA表达,Western印迹检测FLCN、Beclin1、LC3Ⅱ/Ⅰ水平及腺苷酸激活蛋白激酶（AMPK）、哺乳动物雷帕霉素靶蛋白（mTOR）的磷酸化水平。进一步对采用10 ng/ml IFN-γ刺激的黑素细胞感染FLCN抑制病毒进行不同的处理,分为阴性对照组、FLCN抑制组、抑制FLCN及添加mTOR抑制剂的自噬增强组和抑制FLCN及添加AMPK抑制剂的自噬抑制组。采用流式细胞仪检测各组PIG1细胞凋亡,酶联免疫吸附实验检测各组细胞上清液中趋化因子CXCL10和CCL20的浓度。多组间计量资料比较采用单因素方差分析,组间比较采用LSD-t检验。结果 正常原代黑素细胞（0.850 ± 0.120）、白癜风原代黑素细胞（1.507 ± 0.170）和PIG1细胞（0.697 ± 0.130）FLCN蛋白的相对表达差异有统计学意义（F = 50.09,P < 0.001）,白癜风原代黑素细胞高于正常原代黑素细胞和PIG1细胞（t = 4.06、5.89,均P < 0.01）。诱导组FLCN mRNA及蛋白相对表达均高于对照组（均P < 0.01）,LC3Ⅱ、Beclin mRNA及蛋白相对表达均低于对照组（均P < 0.01）;诱导组PIG1细胞LC3Ⅱ/Ⅰ水平（0.72 ± 0.02）、AMPK磷酸化水平（0.714 ± 0.023）低于对照组（1.13 ± 0.02、1.176 ± 0.002,t = 7.34、6.67,均P < 0.01）,mTOR磷酸化水平（1.051 ± 0.023）高于对照组（0.451 ± 0.016,t = 3.81,P = 0.009）。对照组、诱导组及各处理组PIG1细胞凋亡率及CXCL10、CCL20浓度差异均有统计学意义（均P < 0.001）,诱导组高于对照组,FLCN抑制组低于阴性对照组,自噬增强组低于FLCN抑制组,自噬抑制组高于FLCN抑制组（均P < 0.05）。结论 白癜风黑素细胞中高表达FLCN,FLCN表达以及下游信号通路受IFN-γ调控,FLCN可通过调节自噬参与IFN-γ介导的黑素细胞凋亡和趋化因子分泌。     

茶多酚对CD8+T细胞杀伤白癜风患者黑素细胞的保护作用研究

目的 探讨茶多酚对CD8+T细胞杀伤白癜风患者黑素细胞的保护作用.方法 取白癜风患者白斑边缘处皮片组织,培养CD8+T淋巴细胞,细胞纯度用流式细胞仪进行鉴定,通过和黑素细胞共培养验证其针对黑素细胞的杀伤作用.将不同浓度茶多酚加入CD8+T细胞和黑素细胞共培养的体系,用流式细胞仪检测黑素细胞的凋亡.结果 取白癜风皮损边缘表皮组织中成功培养CD8+T淋巴细胞,纯度达90％以上,高表达活化抗原CD137和CD69.CD8+T细胞和黑素细胞共培养后,可明显诱导黑素细胞凋亡.200 μg/ml和400 μg/ml浓度茶多酚处理均可以降低黑素细胞的凋亡率.结论 白癜风皮损边缘组织来源的CD8+T细胞对白癜风患者黑素细胞有明显杀伤作用.茶多酚对抗CD8+T细胞杀伤黑素细胞,从而对黑素细胞有一定的保护作用.     

卡泊三醇对白癜风黑素细胞和CD8＋细胞毒T细胞的影响北大核心CSCD

目的探讨卡泊三醇对白癜风患者黑素细胞及皮损周边CD8＋细胞毒T细胞（CD8＋CTL）增殖及其细胞因子分泌的影响。方法实验分黑素细胞组、CD8＋CTL组、黑素细胞与CD8＋CTL共培养组,细胞计数法检测卡泊三醇处理前后细胞数变化情况,ELISA测定卡泊三醇处理前后分泌白介素6（IL-6）、肿瘤坏死因子α（TNF-α）及干扰素γ（IFN-γ）的变化;细胞计数法检测卡泊三醇处理过的黑素细胞与CD8＋CTL共培养组在添加与不添加抗人IL-6抗体时,黑素细胞及CD8＋CTL数量的变化。筛选10^-8、10^-9mol／L卡泊三醇用于实验。结果在凋亡检测中发现,CD8＋CTL与黑素细胞共培养中黑素细胞有显著凋亡。加卡泊三醇后黑素细胞组的黑素细胞计数与未加药对照组相比,差异无统计学意义（P〉0．05）,而黑素细胞与CD8＋CTL共培养组黑素细胞数明显增加（P〈0．05）;CD8＋CTL组和黑素细胞与CD8＋CTL共培养组的CD8＋CTL细胞数也明显增加（P〈0．05）。与黑素细胞和CD8＋CTL单独培养组相比,黑素细胞与CD8＋CTL共培养组分泌的IL-6、IFN-γ和TNF-α显著减少;经104mol／L卡泊三醇处理后的黑素细胞与CD8＋CTL共培养组分泌的IL-6减少更加明显,与未加药组减少率比较,差异有统计学意义（t=2．89,P〈0．05）,而IFN-γ和TNF-α在加药前后无明显变化（P〉0．05）。在卡泊三醇处理过的共培养组中添加5mg／L抗IL-6抗体后,黑素细胞显著增加,而CD8＋CTL减少,其差异有统计学意义（t=3．53,P〈0．05;t=3．15,P〈0．05）。结论白癜风皮损处的CD8＋CTL对黑素细胞有一定的特异性杀伤作用,卡泊三醇可以减少炎症细胞因子IL-6的分泌,从而减少CD8＋CTL对黑素细胞的杀伤,可能是卡泊三醇治疗白癜风的机制之一。     

NB-UVB对特应性皮炎患者外周血CLA~+CD8~+T细胞的影响

目的观察窄谱中波紫外线(NB-UVB)治疗特应性皮炎(AD)患者的临床疗效,并分析其对外周血皮肤归巢的CD8~+T细胞数量及表达杀伤功能相关蛋白水平的影响,探讨NB-UVB治疗AD的作用机制。方法选取19例AD患者,予NB-UVB照射治疗8周,采用特应性皮炎积分指数(SCORAD)判断病情严重程度;并用流式细胞术检测外周血表达皮肤淋巴细胞相关抗原(cutaneous lymphocyte-associated antigen,CLA)的CD8~+T细胞(CLA~+CD8~+T细胞)的比例,分析其杀伤功能相关蛋白穿孔素、颗粒酶B的表达。另选15例健康体检者作为正常对照。结果 (1)SCORAD评分在AD治疗前组明显高于治疗后组,差异有统计学意义(P0.01);(2)CLA~+CD8~+T细胞的比例在AD治疗前组明显高于对照组,差异有统计学意义(P0.01),且AD治疗前组CLA~+CD8~+T细胞的比例与SCORAD评分正相关(Pearson相关,P0.01);穿孔素和颗粒酶B的表达在AD治疗前组均明显高于对照组,差异均有统计学意义(P均0.01);(3)NB-UVB治疗后,AD患者血清CLA~+CD8~+T细胞的比例较治疗前明显降低,差异有统计学意义(P0.05),且表达穿孔素和颗粒酶B水平也均较治疗前明显下降,差异均有统计学意义(P均0.05)。结论 NB-UVB照射可明显下调AD患者外周血CLA~+CD8~+T细胞的比例及杀伤功能相关蛋白的表达,这可能是NB-UVB治疗AD的机制之一。NB-UVB治疗AD安全有效。     

黄芹素对进展期非节段型白癜风患者外周血CLA~+ CD8~+ T细胞增殖抑制情况的研究

目的探讨具有免疫调节作用的黄芹素对进展期非节段型白癜风患者外周血表达皮肤淋巴细胞相关抗原(cutaneous lymphocyte-associated antigen,CLA)的CD8~+T(CLA~+CD8~+T)细胞增殖是否具有抑制作用。方法以35例进展期非节段型白癜风患者为研究对象,通过免疫磁珠法分选外周血CLA~+CD8~+T细胞,采用CCK-8法检测黄芹素对其外周血CLA~+CD8~+T细胞无杀伤毒性浓度范围,进而研究在此浓度范围内的黄芹素对CLA~+CD8~+T细胞增殖的抑制情况。结果黄芹素能够抑制进展期非节段型白癜风患者外周血CLA~+CD8~+T细胞增殖;使CLA~+CD8~+T细胞分泌IL-2减少,但对IFN-γ的分泌无明显抑制作用;并使细胞周期停滞在G0/G1期。结论黄芹素对进展期非节段型白癜风患者外周血CLA~+CD8~+T细胞具有抑制作用,从免疫学机制方面为黄芹素用于白癜风的治疗提供了实验依据。     

T淋巴细胞在白癜风免疫学发病机制中的研究进展

白癜风是一种皮肤色素脱失性疾病,以表皮功能性黑素细胞破坏为主要特征.目前研究支持其发病与遗传、免疫、氧化应激、神经-体液等机制有关.其中,T淋巴细胞介导的免疫反应在白癜风发病中起重要作用.CD4+T细胞亚群Th1、Th2、Th17、调节性T细胞通过分泌多种细胞因子调节其他免疫细胞的功能、诱导黑素细胞凋亡.CD8+T细胞可经由细胞毒作用直接杀伤黑素细胞.另一方面,自身耐受功能障碍、自身反应性T细胞数量和活性的增加可以增强T细胞对黑素细胞的免疫反应.除此以外,恒定型自然杀伤T细胞、记忆性T细胞等对白癜风免疫相关发病有一定的作用.     

生物制剂治疗白癜风进展

白癜风是一种原因不明的获得性皮肤黏膜色素脱失症，其主要机制为各种原因导致黑素细胞数量或功能的下降。多项研究表明，炎症细胞因子如干扰素（IFN）-γ、白细胞介素（IL）-17、肿瘤坏死因子（TNF）-α、IL-6、IL-8、IL-21、IL-33、磷酸二酯酶（PDE）-4及转化生长因子（TGF）-β）等相互作用，促进了特异性CD8+T细胞定位及杀伤黑素细胞，其中IFN-γ/趋化因子配体（CXCL）10轴被证明在疾病进展上发挥重要作用。针对IFN-γ/CXCL10轴的Janus激酶（JAK）抑制剂以及PDE-4抑制剂的疗效已经得到了临床证实；但TNF-α和IL-17抑制剂的临床疗效尚不明确；基础研究表明IL-10对黑素细胞有保护作用；此外，针对其他靶点的治疗展现出了良好的前景。靶向治疗已经成为了白癜风研究领域的热点。该文对目前生物制剂靶向治疗白癜风的进展作一综述。     

人真皮间充质干细胞对白癜风患者皮损周围CD8+ T淋巴细胞表达和分泌白介素13的影响

【摘要】 目的 探讨人真皮间充质干细胞（DMSC）对白癜风患者皮损周围CD8+ T淋巴细胞分泌表达白介素（IL）13的影响。 方法 细胞增殖检测法（MTS）检测重组IL-13（rIL-13）对黑素细胞增殖的影响。逆转录聚合酶链反应（RT-PCR）和Western印迹法分别检测6例进展期寻常型白癜风患者皮损周围及外周血中CD8+ T淋巴细胞中IL-13基因和蛋白表达。实时荧光定量反转录聚合酶链反应（qRT-PCR）技术和酶联免疫吸附试验（ELISA）分别检测DMSC与白癜风患者皮损周围CD8+ T淋巴细胞共培养前后细胞IL-13 mRNA水平和上清蛋白水平。 结果 不同浓度（10、50、100、250、500 μg/L）的rIL-13作用黑素细胞24、48、72、96 h后黑素细胞的增殖与对照组比较均未见明显变化（均P > 0.05）。白癜风患者皮损周围及外周血中CD8+ T淋巴细胞均可表达IL-13,但皮损周围CD8+ T淋巴细胞表达IL-13更显著。将皮损周围CD8+ T淋巴细胞和DMSC共培养,CD8+ T淋巴细胞IL-13 mRNA（0.100 0 ± 0.002 4）和蛋白［（1 509.62 ± 48.44） ng/L］的表达水平均显著低于单独培养的CD8+ T淋巴细胞［mRNA：0.383 2 ± 0.018 7,蛋白：（5 507.98 ± 34.11） ng/L,均P < 0.05］。 结论 白癜风患者皮损周围CD8+ T淋巴细胞高表达IL-13,DMSC能够有效地抑制其表达IL-13,或许可作为白癜风的治疗靶点之一。     

4-Tertiary butyl phenol exposure sensitizes human melanocytes to dendritic cell-mediated killing: relevance to vitiligo

The trigger initiating an autoimmune response against melanocytes in vitiligo remains unclear. Patients frequently experience stress to the skin prior to depigmentation. 4-tertiary butyl phenol (4-TBP) was used as a model compound to study the effects of stress on melanocytes. Heat shock protein (HSP)70 generated and secreted in response to 4-TBP was quantified. The protective potential of stress proteins generated following 4-TBP exposure was examined. It was studied whether HSP70 favors dendritic cell (DC) effector functions as well. Melanocytes were more sensitive to 4-TBP than fibroblasts, and HSP70 generated in response to 4-TBP exposure was partially released into the medium by immortalized vitiligo melanocyte cell line PIG3V. Stress protein HSP70 in turn induced membrane tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression and activation of DC effector functions towards stressed melanocytes. Melanocytes exposed to 4-TBP demonstrated elevated TRAIL death receptor expression. DC effector functions were partially inhibited by blocking antibodies to TRAIL. TRAIL expression and infiltration by CD11c+ cells was abundant in perilesional vitiligo skin. Stressed melanocytes may mediate DC activation through release of HSP70, and DC effector functions appear to play a previously unappreciated role in progressive vitiligo.     

Fas-FasL interaction in cytotoxic T cell-mediated vitiligo: The role of lesional expression of tumor necrosis factor-α and interferon-γ in Fas-mediated melanocyte apoptosis

Vitiligo is an acquired skin depigmentation disorder resulting from the selective loss of epidermal melanocytes, and previous studies have suggested that a T lymphocyte-mediated mechanism has a role in melanocyte loss. Although Fas-Fas ligand (FasL) interactions are important for T lymphocytes to mediate cytotoxicity, there are only few reports examining the involvement of the Fas-FasL pathway in vitiligo using in vivo mouse models. In addition, there have been no reports concerning Fas-mediated apoptosis in human melanocytes in vitro. In this study, we found that the Fas-mediated pathway is involved in cytotoxic T lymphocyte (CTL)-dependent vitiligo in a mouse model and FasL-induced apoptosis of human melanocytes. Tumor necrosis factor (TNF)-α and interferon (IFN)-γ, the expression levels of which have been reported to be elevated in lesional skin of patients with vitiligo, synergistically upregulated Fas expression on human melanocytes but inhibited the Fas-mediated apoptosis. Treatment with TNF-α and IFN-γ synergistically upregulated the expression of the anti-apoptotic genes, c-IAP2, c-FLIP and MCL1. A siRNA knock-down study showed that c-FLIP and MCL1, but not c-IAP2, were involved in inducing synergistic inhibitory effects on Fas-mediated apoptosis. Furthermore, we found that FasL and TNF-related apoptosis - inducing ligand (TRAIL) synergistically induced apoptosis on human melanocytes. In conclusion, our results suggest that the Fas-FasL pathway is involved in CTL-dependent vitiligo and the elevated expression levels of TNF-α and IFN-γ in lesional skin may act synergistically on melanocytes to suppress Fas-mediated apoptosis.     

Perforin and granzyme B may contribute to skin inflammation in atopic dermatitis and psoriasis

BACKGROUND: Infiltration of the skin by pathogenic T cells is regarded as a key factor in the development of inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. OBJECTIVES: To investigate whether T cells containing cytotoxic proteins may contribute to the generation of skin inflammation in these skin diseases. METHODS: Skin biopsy specimens were obtained from non-lesional and lesional skin of patients with chronic AD (n = 8) and psoriasis (n = 6), and from non-atopic controls with normal skin (n = 6). Expression of perforin and granzyme B was investigated by immunohistochemistry. RESULTS: A significant enhancement of perforin and granzyme B expression was observed in lesional AD skin as compared with normal skin, non-lesional AD skin and psoriasis. Expression of these cytotoxic proteins was also increased in psoriasis as compared with normal skin and non-lesional psoriatic skin. Immunoreactivity for perforin and granzyme B was mainly found in the cytoplasm of lymphocytic cells located in the perivascular infiltrate. In AD increased numbers of positive cells were also observed focally at sites of spongiosis in the epidermis. Double immunostaining revealed that both CD4+ and CD8+ T cells are capable of expressing perforin and granzyme B. CONCLUSIONS: Our data suggest that cytotoxic CD4+ and CD8+ T cells containing perforin and granzyme B may play an integral part in eliciting cutaneous inflammation in AD.     

Reduction of skin-homing cytotoxic T cells (CD8+ -CLA+) in patients with vitiligo

Background: Vitiligo is a frequently acquired, hereditary disease, characterized by achromic macules due to the absence of melanocytes. In contrast with earlier studies, in which the main pathogenic role was attributed to anti‐melanocyte antibodies, recent papers have emphasized a role for CD8⁺ cytotoxic T lymphocytes in melanocyte destruction. Fifteen percent of peripheral T cell express cutaneous lymphocyte‐associated antigen (CLA), responsible for skin‐homing T cell. Phototherapy is used to treat patients with generalized vitiligo and it has been shown to interfere with CLA⁺ T cells in other skin diseases. Objective: To describe peripheral blood T cell subpopulations' frequency and ability to express the skin‐homing molecule (CLA) in patients with non‐segmental vitiligo, before and after photochemotherapy (PUVA). Patients and Methods: Twenty‐two patients with generalized and active spreading vitiligo were submitted to 30 PUVA‐8MOP sessions. Lymphocyte immunophenotyping was performed by flow cytometry using anti‐CD3, anti‐CD8 and anti‐CLA monoclonal antibodies. Fifteen healthy volunteers, sex‐ and age‐matched, were included as a control group. Results: CD8⁺–CLA⁺ T cells were significantly reduced in number in untreated vitiligo patients (P=0.008) when compared with control individuals, albeit with a more intense CLA expression (P=0.028). These findings were not altered after PUVA. No significant difference was noticed in CD4/CD8 ratios nor in CD4–CLA⁺ T cell numbers between vitiligo patients and controls, both before and after PUVA. Conclusions: CD8–CLA⁺ T cells are reduced in peripheral blood of patients with non‐segmental vitiligo. This finding may be related to the previously reported increase of CD8⁺ cells in both lesions and perilesional skin of these patients.     

Th17细胞与白癜风的发病机制

白癜风是一种常见的皮肤病,其原因是皮肤黑素细胞的缺失。黑素细胞缺失的确切机制尚不清楚,研究指出,细胞免疫在白癜风发病机制中起到重要作用。在某些特定细胞因子的作用下,CD4＋T细胞分化为Th17细胞,Th17细胞可参与多种疾病的发病。在白癜风发病过程中,Thl7细胞和树突细胞数量增多,功能活跃。Th17细胞除主要分泌IL-17外,还分泌IL-6、IL-21、IL-22和肿瘤坏死因子d等细胞因子,他们参与白癜风发病,导致黑素细胞生成减少、萎缩、消失,黑素生成减少,最终形成白癜风。     

特应性皮炎患者外周血皮肤归巢的CD8+ T细胞研究

【摘要】 目的 探讨特应性皮炎（AD）患者外周血CD8+ T细胞皮肤归巢及杀伤功能相关蛋白的表达。 方法 15例AD患者和14例健康人,用流式细胞仪,检测外周血CD8+ T细胞、表达皮肤淋巴细胞相关抗原的CD8+ T细胞（CLA+CD8+ T细胞）的比例。 结果 CD8+ T细胞比例在AD组和对照组之间差异无统计学意义（P > 0.05）;CD8+ T细胞穿孔素、颗粒酶B和FasL的表达在两组间差异亦无统计学意义（均P > 0.05）。CLA+CD8+ T细胞比例在AD组（3.80% ± 1.46%）高于健康对照组（2.18% ± 0.85%）（t = 3.636,P < 0.01）,AD组CLA+CD8+ T细胞比例与SCORAD（SCORing of Atopic Dermatitis）评分呈正相关（r = 0.565,P < 0.05）;CCR4在CD8+ T细胞表达在AD组（13.86% ± 4.42%）高于健康对照组（9.50% ± 2.14%）（t = 3.738,P < 0.01）,而CCR10和CXCR6的表达在两组间差异均无统计学意义（P > 0.05）。CLA+CD8+ T细胞穿孔素的表达在AD组（74.27% ± 15.94%）高于健康对照组（57.20% ± 14.64%）（t = 2.998,P < 0.01）,颗粒酶B的表达在AD组（70.90% ± 13.85%）也高于健康对照组（56.41% ± 11.00%）（t = 3.104,P < 0.01）,而FasL的表达在两组间差异无统计学意义（P > 0.05）。CLA+CD8+ T细胞CCR4、CCR10和CXCR6的表达在AD组与对照组间差异无统计学意义（均P > 0.05）。 结论 AD患者外周血CLA+CD8+ T细胞数量增加,杀伤功能相关蛋白穿孔素、颗粒酶B的表达增强,可能参与了AD的发病。     

Characterization of cytotoxic immune response in skin and mucosal lesions of paracoccidioidomycosis

Background: CD8+ T cells and natural killer (NK) cells are involved in the immune response against some pathogens. For this purpose, we investigated the in situ paracoccidioidomycosis (PCM) immune response addressing the participation of NK cells, CD8+ T cells, perforin and granzyme B expression. Methods: Sixty biopsies of PCM skin and mucosa were classified according to the presence of compact granulomas (G1), poorly organized granulomas (G2) and both kinds in the same lesion (G3). CD8+ T cells, NK cells, perforin and granzyme B were showed by immunohistochemistry. Results: CD8+ T cells were increased over NK cells in cutaneous G1 and G2 lesions. There was no difference regarding such cells in G3 lesions, although they were abundant in such lesions. In mucosa, CD8+ T cells were increased in number over NK cells in all groups. Granzyme B in skin increased in G2 and G3. The number of granzyme did not differ in mucosal lesions in the three groups. Conclusions: CD8+ T cells and NK cells play a role in PCM cutaneous and mucosal lesions. The predominance of CD8+ T cells over NK cells may represent an effective response against the fungi. Moreover, the high number of granzyme B expressing cells corroborates this possibility. Pagliari C, Pereira NV, Kanashiro L, Stegun FW, Croda J, Seixas Duarte MI, Sotto MN. Characterization of cytotoxic immune response in skin and mucosal lesions of paracoccidioidomycosis.     

白癜风患者皮损中CD4~+,CD8~+T淋巴细胞及朗格汉斯细胞的检测

目的探讨白癜风患者皮损中CD4+,CD8+T淋巴细胞、朗格汉斯细胞(LC)及黑素细胞(MC)在白癜风发病中的作用。方法采用Envision免疫组化染色法,对12例白癜风进展期患者和9例稳定期患者皮损处CD4+,CD8+T淋巴细胞、LC及MC进行检测,并与10例正常人皮肤进行对照。结果白癜风患者皮损中CD4+,CD8+T淋巴细胞、LC表达较对照组显著增多(P<0.01),而MC表达较对照组显著减少(P<0.01)。结论白癜风患者皮损中LC,CD4+,CD8+T淋巴细胞异常表达可能参与白癜风的发病,其作用模式可能是LC抗原递呈,CD4+,CD8+T淋巴细胞浸润破坏或攻击MC,从而引起白癜风患者表皮基底层的MC减少或消失,导致白癜风的发生。