Identification of lesional CD4+ CD25+ Foxp3+ regulatory T cells in Psoriasis

BACKGROUND: Depletion of CD4+ CD25+ Foxp3+ naturally occurring regulatory T cells (T(reg)) induces autoimmune phenomena. These cells have not yet been fully characterized in the skin of psoriatic patients. OBJECTIVES: To prove that the Zenon immunofluorescent labeling technique is suitable for the demonstration of co-localization of T-cell markers and in particular to show the distribution of T(reg) in psoriatic skin. METHODS: In biopsies derived from normal and psoriatic skin, CD4+ CD25+, CD4+ CD45RO+, CD8+ CD25+, CD8+ CD45RO+ and CD4+ CD25+ Foxp3+ cells in the dermis and in the epidermis were immunophenotyped, using a quantitative immunofluorescent labeling technique (Zenon), analyzed and compared using image analysis. RESULTS: The immunofluorescent labeling technique was shown to be an easy and reliable tool to demonstrate co-localization of T-cell markers. In psoriasis, all pathogenic T-cell subsets (CD4+ CD25+, CD4+ CD45RO+, CD8+ CD25+ and CD8+ CD45RO+ cells) were significantly increased in the dermis and in the epidermis, as compared to normal skin (all p < 0.05). Using this labeling technique we were able to reveal CD4+ CD25+ Foxp3+ T(reg) in psoriatic dermis, but not in the dermis of normal skin (p < 0.0001). CONCLUSIONS: The Zenon immunofluorescence technique in combination with image analysis is suitable for the demonstration of co-localization of T-cell markers in tissue. Increased numbers of pathogenic T cells (CD4+ CD25+, CD4+ CD45RO+, CD8+ CD25+ and CD8+ CD45RO+) were shown in the dermis and epidermis, whereas CD4+ CD25+ Foxp3+ T(reg) were identified in psoriatic skin with a predilection for the upper dermis.     

高效抗逆转录病毒疗法治疗HIV-1感染者的免疫学变化

目的 探讨高效抗逆转录病毒疗法(HAART)对人免疫缺陷病毒1型(HIV-1)感染者免疫重建和部分免疫激活标志变化的影响。方法 37例HIV-1感染者,经两种核苷类逆转录酶抑制剂和一种非核苷类逆转录酶抑制剂组方的HAART一年治疗,分别在治疗前、治疗12周、24周和48周,检测其血浆HIV-1病毒载量、CD3⁺CD4⁺、CD3⁺CD8⁺、CD4⁺CD45RA⁺CD62L⁺、CD4⁺CD45RO⁺、CD8⁺CD38⁺、CD4⁺CD28⁺、CD8⁺CD28⁺细胞数和血浆可溶性的CD27(sCD27)分子水平。结果 HIV-1病毒载量的变化与CD3⁺CD4⁺淋巴细胞计数、CD4⁺CD28⁺、CD8⁺CD28⁺细胞计数和百分比呈明显的负相关关系;与CD8⁺CD38⁺细胞计数和百分比、sCD27水平呈明显的正相关关系。抗病毒效果好的完全应答组上述各项检测指标比抗病毒效果差的部分应答组显示出更显著的变化。结论 CD8⁺CD38⁺、CD4⁺CD28⁺、CD8⁺CD28⁺细胞计数和百分比以及sCD27水平与病毒载量在HAART治疗中显示同步变化,是观察抗病毒效果和免疫学效果的指标。     

Lymphocyte subsets in peripheral blood of patients with psoriasis before and after treatment with leishmania antigens

Peripheral blood mononuclear cells (PBMC) collected from subjects prior to treatment and post-treatment with a vaccine composed of leishmania antigens were analyzed by flow cytometry. Upon analysis, it was noticed that lymphocyte subsets (LS) varied with psoriasis area and severity index (PASI) range (1–10, 11–20 and 21–72). Pre-treatment absolute values of gated LS were as follows. CD4+CD8−, CD3+CD8−, CD8+CD3+, CD8+CD4− and CD8+HLA− decreased in PBMC as PASI increased, suggesting migration from the blood to the skin. Contrary to the previous finding, the following LS, CD8+HLA+ and HLA+CD8−, and membrane surface immunoglobulin IgA+, IgD+ and IgM+ increased in PBMC as PASI increased, suggesting activation and proliferation by unknown antigens. After treatment with seven doses of AS100, the following LS, CD3+CD8−, CD8+CD3−, HLA+CD8−, CD8+HLA+ and CD4+CD8−, increased, while CD8+CD3+, CD8+HLA−, CD19 and CD8+CD4+ decreased in PBMC.     

Comparative immunophenotypic study of lichen sclerosus: epidermotropic CD57+ lymphocytes are numerous--implications for pathogenesis

To characterize the immunophenotype of inflammatory cells in lichen sclerosus (LS), we performed a comparative case control study using one- and two-color immunohistochemistry and the nitro blue tetrazolium (NBT) reaction. Study material consisted of 100 biopsies from patients with LS or from 12 control groups consisting of inflammatory, scarring, and depigmenting cutaneous disorders. In addition, fresh tissue was sampled from four vulvectomy specimens for NBT testing. The typical inflammatory infiltrate of LS contained numerous epidermotropic CD3+, CD8+, CD57+ cells, increased intraepidermal HLA-DR+ cells, and a dermal infiltrate rich in CD8+, CD57+, HLA-DR+, and CD68+ inflammatory cells. Comparing LS to the 12 control groups, epidermotropic CD57+ lymphocytes independently predicted LS (P = 0.006, logistic regression, multivariate analysis). Among the 12 control groups, only specimens of the inflammatory stage of morphea exhibited numerous dermal CD57+ lymphocytes. Two-color immunohistochemistry confirmed the CD3+/CD8+CD57+ and CD3+/ CD8+/CD57+HLA-DR+ epidermotropic and dermal lymphocytic phenotypes and the dermal macrophage CD68+HLA-DR+ phenotype. In LS, the NBT reaction revealed evidence of superoxide production associated with CD68+HLA-DR+ cells. Expansion of CD8+CD57+lymphocytes is associated with viral infections, autoimmune disease, malignancies, and transplantation and is suspected to be the result of chronic excessive antigen challenge. In these pathologic states, CD8+CD57+ lymphocytes (as terminally differentiated, antigen-specific T cells) participate in the suppression of cytolytic activity to limit tissue damage. In LS, activated macrophages and lymphocytes indicate persistent antigen-driven inflammation. LS's numerous CD8+CD57+ lymphocytes may be either the mediators or the consequence of its hallmark sclerosis.     

尖锐湿疣患者活化自然杀伤细胞的检测

目的 :检测尖锐湿疣 (CA)患者外周血NK细胞 (CD5 6+ )及活化NK细胞 (CD5 6+ CD69+ ) ,并探讨它们在CA发病中的作用。方法 :采用免疫荧光三标记流式细胞术检测 3 0例CA患者外周血CD5 6+和CD5 6+ CD69+ 细胞 ,同时以 3 1例正常人作为对照。结果 :CA患者外周血CD5 6+ 和CD5 6+ CD69+ 细胞百分率均显著高于正常对照组 (均为P <0 0 0 1 ) ,长病程组和短病程组之间差异无显著性。结论 :CA患者外周血CD5 6+ 和CD5 6+ CD69+ 细胞百分率显著增高 ,说明NK细胞在CA发病中起着非特异性抗病毒免疫的重要作用。     

Profiles of activated T lymphocytes in peripheral blood of Kuwaiti psoriasis vulgaris patients

We have previously reported unexpected immunological features of psoriasis among Kuwaitis, suggesting novel patterns of immune reactivity contributing to the disease. To better define this phenomenon, we herein describe profiles of major populations and immunologically activated subsets of peripheral blood lymphocytes in a cohort of Kuwaiti psoriasis vulgaris patients. Whole venous blood from fifteen psoriatic and twenty eight normal, healthy subjects was analyzed by 2-color flow cytometry for levels of major lymphocyte species and their immunologically activated subsets. When compared to normal subjects, psoriatic blood contained lower cell densities of CD2+, CD8+ (p=0.002 respectively) and B lymphocytes (CD19+) (p=0.003), with a trend toward a lower CD4+ density (p=0.072). Within each major lymphocyte population, activated lymphocytes were present at higher percentages in psoriatic than in healthy blood. These included CD4+ HLA-DR+ (p=0.002), CD4+CD25+ (p=0.043), CD4+CD54+ (p=0.005), CD8+CD25+ (p=0.015), CD8+ HLA-DR+ (p=0.046) and CD3+CD16+CD56+ (p=0.023) Additionally, psoriatic patients were found to have an expanded ratio of memory to naive T cells (CD45RO+CD45RA+) relative to control subjects; this was expected on the basis of increased immune activation. Our findings are consistent with a picture of psoriasis as a disease mediated by activated lymphocytes.     

系统性红斑狼疮患者T淋巴细胞CD70基因表达及其启动子区域甲基化状态的研究

目的 探讨系统性红斑狼疮（SLE）患者T淋巴细胞CD70mRNA和蛋白的表达及CD70基因启动子DNA甲基化的状态。方法 分离15例活动期SLE患者、15例非活动期SLE患者和15例健康对照外周血CD4+与CD8+细胞,用实时定量逆转录PCR（RT-PCR）方法检测CD4+和CD8+细胞CD70 mRNA转录水平,流式细胞仪检测CD4+CD70+ 细胞和CD8+CD70+细胞百分率,亚硫酸氢钠基因测序法检测CD4+细胞和CD8+细胞CD70基因启动子区域甲基化水平。组间比较采用单因素方差分析,组间两两比较采用SNK-q检验。 结果 ①活动期、非活动期SLE患者CD4+细胞CD70 mRNA转录水平分别为0.82 ± 0.12和0.73 ± 0.11,明显高于健康对照组（0.45 ± 0.09）,F = 53.017,P < 0.01,活动期SLE患者CD4+细胞的CD70 mRNA转录水平显著高于非活动期SLE患者（P < 0.05）。活动期、非活动期SLE患者外周血CD4+CD70+细胞百分率分别为80.30% ± 11.04% 和66.80% ± 3.98%,明显高于健康对照组（12.48% ± 3.45%）,F = 311.517,P < 0．01,活动期SLE患者CD4+CD70+细胞百分率显著高于非活动期SLE患者（P值 < 0.05）。SLE患者外周血CD70+CD4+细胞百分率与SLE疾病活动度呈显著正相关（r = 0.792,P = 0.000）。活动期、非活动期SLE患者组的CD4+细胞CD70基因启动子序列-600 ~ -300 bp 区域平均甲基化水平分别为0.32 ± 0.05和0.36 ± 0.05,明显低于健康对照组（0.62 ± 0.05）,F = 152.64,P < 0.01,活动期平均甲基化水平明显低于非活动期SLE患者组（P < 0.05）。结论 CD4+细胞CD70基因启动子区域处于低甲基化状态,这种低甲基化状态可能是CD70过度表达的直接原因。     

Circulating CD4+ CD25brightFOXP3+ regulatory T-cells are significantly reduced in bullous pemphigoid patients

Bullous pemphigoid (BP) is the most frequent autoimmune bullous skin disease, characterised by auto-antibodies against the hemidesmosome complex. Recently, regulatory T cells (Tregs) have been implicated in the development of several autoimmune diseases; few data are available in BP, failing to demonstrate a role of this subset in disease pathogenesis. The aim of this study was to investigate the expression and phenotypes of different Tregs (CD4+ CD25brightFOXP3+ and CD8+ CD28- cells) in BP to clarify whether the depletion of this subset constitutes one mechanism of tolerance loss. The CD4+ CD25brightFOXP3 and CD8+ CD28- circulating subsets were determined by flow-cytometry in 26 untreated BP patients and compared with a group of age- and sex-matched healthy controls (HC, n?=?30). Absolute and percentage values of the CD4+ CD25brightFOXP3+ cells were significantly reduced in BP compared with HC (median CD25brightFOXP3+ expression within CD4+ cells: 1.8 vs. 3.5%, p?=?0.002); conversely, BP patients were characterised by a significant expansion of the CD25brightFOXP3- "activated" T-cell subset. CCR4 and CD62L were expressed on the majority of CD4+ CD25brightFOXP3+ cells (75.2 and 82.3%, respectively). No differences in the CD8+ CD28- subset were found between BP and HC. This is the first report showing a significant reduction of circulating CD4+ CD25brightFOXP3+ Treg frequency in BP patients.     

Functional characterization of CD4+CD25+ regulatory T cells differentiated in vitro from bone marrow-derived haematopoietic cells of psoriasis patients with a family history of the disorder

BACKGROUND: In psoriasis CD4+CD25+ regulatory T cells are functionally deficient. The imbalance between regulatory and effector T-cell functions is important for inducing psoriasis. It is reasonable to speculate that the dysfunctional activity of CD4+CD25+ regulatory cells may originate partly from the abnormal haematopoietic cells determined mainly by genetic background. OBJECTIVES: To test the hypothesis that haematopoietic stem cells are responsible for dysfunctional CD4+CD25+ regulatory cells in psoriasis. METHODS: Bone marrow-derived CD34+ haematopoietic cells from patients with psoriasis (with a family history of psoriasis) and from normal controls were differentiated into T cells in vitro. CD4+CD25+ T cells were isolated by an immunomagnetic bead method, and proliferation activity and capacity for cytokine secretion were determined. Furthermore, the ability of CD4+CD25+ T cells to suppress the proliferative responses of allogeneous peripheral blood CD4+CD25- effector T cells was assessed in vitro. RESULTS: The differentiated CD4+CD25+ T cells of psoriatic origin showed similar characteristics to those of normal volunteers, including proliferation activity and secretion profile of the cytokines interleukin (IL)-2, IL-4, IL-8, IL-10 and interferon (IFN)-gamma. However, proliferation and secretion levels of the cytokines IL-2 and IL-10 for CD4+CD25+ cells of psoriatic CD34+ cell origin were significantly lower than those of normal controls in response to streptococcal superantigen (Strep-A). In particular, CD4+CD25+ T cells differentiated from psoriatic CD34+ cells were functionally insufficient to restrain effector T-cell proliferation. CONCLUSIONS: CD4+CD25+ T cells differentiated in vitro from haematopoietic cells of patients with psoriasis are impaired in regulatory function. The dysfunction of psoriatic CD4+CD25+ T cells may be due to inherent genetic programming passed down from bone marrow-derived haematopoietic cells.     

Frequency, function and CLA expression of CD4+CD25+FOXP3+ regulatory T cells in bullous pemphigoid

Bullous pemphigoid (BP) is an autoimmune blistering skin disease associated with autoantibodies to collagen XVII and tissue-separation along the dermo-epidermal junction. We addressed the question whether the loss of tolerance in BP patients is associated with a reduction and/or functional impairment of CD4+CD25+FOXP3+ regulatory T cells, which are essential for the active maintenance of self tolerance. The relative and absolute frequency of CD4+CD25+ and CD4+CD25(high) regulatory T cells in the peripheral blood of newly diagnosed, untreated patients was similar to that of healthy controls. Interestingly, more than 50% of circulating CD4+CD25(high) regulatory T cells from both patients as well as healthy controls expressed cutaneous lymphocyte-associated antigen. Considerable numbers of FOXP3+ cells were detected in lesional skin of patients. CD4+CD25+ regulatory T cells of patients were functionally intact as assessed by their ability to suppress allogeneic as well as antigen-specific T-cell proliferation. These data argue against a general defect of CD4+CD25+FOXP3+ regulatory T cells in patients with BP.     

Agranular CD4+ CD56+ hematodermic neoplasm: a new case report

BACKGROUND: "Agranular CD4+ CD56+ hematodermic neoplasm" are rare hematologic neoplasms which were recently shown to correspond to the plasmocytoid dendritic cells. CASE REPORT: A 83-year-old presented isolated skin lesions purple, infiltrating the dermis. The biopsy has shown a dense dermal infiltration with malignant cells CD4+ CD56+ CD43+. There were no bone marrow involvement and no circulating blood cells. A chemotherapy permitted a clinical remission after six courses. Unfortunately, skin and blood relapses appear four months later. After a short success of chemotherapy by DHAP, the patient died three month later. DISCUSSION: "Agranular CD4+ CD56+ hematodermic neoplasm" is a distinct entity from the cutaneous primary lymphomas. Recently plasmocytoid monocyte cells have been identified as the precursor of the malignant population with the high expression of CD123, IL3 receptor. It is a distinct clinicopathologic entity by its clinical presentation with skin tropism, bone marrow involvement with or without leukemic phase and poor prognosis independent of the kind of treatment and its particular phenotype CD4+ CD56+ CD43+. It would be interesting to use antibodies linked to CD123 in therapeutic because any treatment have efficacity in this disease.     

Mediation of alopecia areata by cooperation between CD4+ and CD8+ T lymphocytes: transfer to human scalp explants on Prkdc(scid) mice

OBJECTIVE: To determine the role of CD4+ and CD8+ T lymphocytes in the pathogenesis of alopecia areata. DESIGN: Relapse of alopecia areata was induced in autologous human scalp grafts on Prkdc(scid) mice by injection of activated T lymphocytes derived from lesional skin. CD4+ and CD8+ T cells were separated by magnetic beads before injection. SETTING: University-based dermatology practice. PARTICIPANTS: Eleven patients with either alopecia totalis or severe alopecia areata. MAIN OUTCOME MEASURES: Hair regrowth, hair loss, and immunohistochemical findings of scalp explants. INTERVENTION: Transfer of scalp T cells to autologous lesional scalp explants on Prkdc(scid) mice. RESULTS: Injection of unseparated T cells and mixed CD4+ plus CD8+ T cells resulted in significant hair loss (P<.01) in 5 of 5 experiments. However, injection of purified CD4+ or CD8+ T cells alone did not result in reproducible hair loss. CD4+ and CD8+ T cells induced follicular expression of intercellular adhesion molecule 1 (CD54), HLA-DR, and HLA-A, HLA-B, and HLA-C after injection into scalp grafts. CONCLUSIONS: CD4+ and CD8+ T cells have a role in the pathogenesis of alopecia areata. It is hypothesized that CD8+ T cells act as the effector cells, with CD4+ T cell help. It is now necessary to look for HLA-A, HLA-B, and HLA-C associations with alopecia areata. Therapeutic manipulations that interfere with CD8+ activity should be examined.     

特应性皮炎患者外周血CD4+CD25+调节性T细胞的检测

目的 探讨CD4+CD25+调节性T细胞（CD4+CD25+ Treg）在特应性皮炎（AD）发病中的作用机制及临床意义。方法 流式细胞仪分析AD患者外周血中CD4+CD25+ Treg细胞数量,实时荧光定量PCR检测外周血单核细胞（PBMC）中Foxp3 mRNA水平,ELISA检测血清中IL-2、IL-4、IL-10、IFN-γ水平。结果 AD患者外周血中CD4+CD25+ Treg细胞占CD3+ T细胞及CD4+ T细胞的比例均明显低于正常人对照组（t′ = 3.775、4.533,P值均 ＜ 0.01）;外周血中CD4+CD25+ Treg细胞占CD3+ T细胞比例在AD患者急性期明显低于慢性期（t = 2.217,P < 0.05）,而在急性期与亚急性期、亚急性期与慢性期之间差异均无统计学意义（t = 1.558、0.49,P值均 ＞ 0.05）。AD患者PBMC中Foxp3 mRNA的水平低于正常人对照组（z = -2.368,P ＜ 0.05）;其外周血中CD4+CD25+ Treg细胞与血清中IL-2和IL-10成正相关（r = 0.512、0.494,P值均 ＜ 0.05）,与IL-4和IFN-γ的相关性无统计学意义（r = -0.110、-0.237,P值均 ＞ 0.05）。结论 在AD患者中,外周血中CD4+CD25+ Treg细胞数量及Foxp3 mRNA水平均下降,从而可能减少对Th2细胞增生及其细胞因子分泌的抑制,使Th2占优势,参与AD的发病。     

Antigens from Leishmania amastigotes inducing clinical remission of psoriatic arthritis

A first generation vaccine (AS100-1) was manufactured with protein from four cultured Leishmania species, which proved to be effective in the treatment of psoriasis. A single blind trial on 3,132 psoriasis patients revealed 508 (16.2%) subjects with psoriatic arthritis (PsA) that received AS100-1 antigens. The study group was distributed according to percent psoriasis area and severity index (PASI) reduction from PASI 10 to PASI 100. All groups decreased in arthritis score (AS), tender joints counts and nail changes after treatment; the highest decreased in the PASI 100 group. Relapses of psoriasis and PsA had PASI and AS lower than initial values before treatment. Clinical remissions were at lower doses and less time, after the second course of treatment. Peripheral blood mononuclear cells (PBMC) lymphocyte subsets (LS) varied with PASI range (1–10, 11–20 and 21–72). Pre-treatment, absolute values of gated LS: CD4+, CD8+HLA−, CD8+HLA+, CD8+CD3−, CD8+CD3+ decreased in PBMC as PASI increased, suggesting migration from the blood to the skin. In contrary to the previous finding, the following LS: CD8+CD4−, CD3+CD8−, HLA+CD8−, CD19, CD8+CD4+ and membrane surface immunoglobulin IgA+, IgD+, IgM+, IgE+, and IgG+ increased in PBMC as PASI increased suggesting activation and proliferation by unknown antigens creating a homeostatic cycle between skin/joints and peripheral blood. After nine doses of AS100-1, the following LS: CD8+CD3+, CD8+HLA+, CD3+CD8−, CD4+CD8−, CD8+HLA−, HLA+CD8−, CD8+CD3−, CD19+, CD8+CD4−, CD8+CD4+, IgA+, IgD+, IgM+, IgE+, and IgG+ decreased significantly as compared with values before treatment. The LS decreased stops the vicious cycle between skin/joints and blood explaining clinical remission of lesions.     

Relative impact of CD4+CD25+ regulatory T cells and tacrolimus on inhibition of T-cell proliferation in patients with atopic dermatitis

BACKGROUND: It has been established recently that CD4+CD25+ regulatory T cells (Tregs) play an important role in controlling various immune responses. Immunosuppressive drugs are often used to treat immune dysregulation but are frequently associated with undesirable side-effects. OBJECTIVES: We examined the suppressive capacity of circulating Tregs in patients with atopic dermatitis (AD). Combined effects of Tregs and tacrolimus on the inhibition of T-cell proliferation in vitro were also assessed. METHODS: CD4+CD25+ and CD4+CD25- T cells were isolated from peripheral blood mononuclear cells using immunomagnetic beads. CD4+CD25- T cells were stimulated with purified protein derivative (PPD) or house dust mite allergen (Der p1) for 6 or 7 days, respectively. A dose range of tacrolimus and CD4+CD25+ T cells were added separately, or together. Proliferation was measured by (3)H-thymidine incorporation. RESULTS: CD4+CD25+ T cells from normal controls and patients with AD are anergic and inhibit the proliferation of CD4+CD25- T cells in response to PPD and Der p1 in vitro in a dose-dependent manner. Addition of tacrolimus and Tregs together showed significantly stronger inhibition of proliferation than either on their own. This was true for both antigens and both in normal controls and in patients with AD. CONCLUSIONS: CD4+CD25+ T cells in patients with AD have normal suppressive activity compared with healthy controls. Tregs and tacrolimus have additive effects on the inhibition of proliferation in response to PPD and Der p1.     

Selective changes in lymphocytic differentiation antigens in the peripheral blood of patients with alopecia areata treated with oral zinc

Recent research has shown that the regrowth of hair in alopecia areata (AA) is associated with the normalization of the CD4+/CD8+ ratio, which is usually in an unbalanced state. This dysbalance is represented by an increased level of CD4+ and a decrease of CD8+ cells and found not only in the bulbar region but also in the peripheral blood. Since zinc generally acts as a polyclonal T-cell activator and has been proved a useful oral therapeutic in AA, we additionally controlled the levels of CD4+ and CD8+ cells as well as other lymphocyte subpopulations in the peripheral blood of AA patients before and during oral treatment with zinc. Our data revealed a significant raise of CD3+, CD8+, CD19+, HLA-DQ+, HLA-DR+, and Leu 2a+8+ cells during oral therapy with zinc. We conclude that the successful treatment of AA with zinc may be due to immunomodulation, especially through the increase of CD8+ cells.     

银屑病患者体外系统血液固有免疫反应中CD4~+ CD25~+ T细胞及CD4~+ CD25~(high) T细胞的变化与意义

目的用体外系统血液固有免疫反应体系研究银屑病患者外周血CD4+ CD25+T细胞及CD4+ CD25highT细胞的变化,并探讨其在银屑病发病机制中的作用。方法将灭活大肠杆菌悬液(3×108/mL)0.2mL作为免疫原激活剂加入枸橼酸抗凝的全血细胞悬液0.2mL和血浆0.3mL中,37℃水浴1h,用流式细胞仪测定CD4+ CD25+T细胞及CD4+ CD25highT细胞的比例。结果在加入大肠杆菌的银屑病全血细胞组(银屑病实验组)CD4+ CD25highT细胞比例(1.88%)明显高于银屑病对照组(1.41%)(P﹤0.01),CD4+ CD25+T细胞及CD4+ CD25highT细胞的比例(16.86%,1.88%)明显低于加入大肠杆菌的健康实验组(24.26%,2.81%)(P﹤0.01);银屑病对照组CD4+ CD25+T细胞及CD4+ CD25highT细胞的比例(15.97%,1.41%)较健康对照组明显降低(21.75%,2.17%)(P﹤0.01);健康实验组CD4+ CD25+T细胞及CD4+ CD25highT细胞的比例群(24.26%,2.81%)均明显高于健康对照组(21.75%,2.17%),(P﹤0.05)。结论银屑病患者CD4+ CD25+T细胞及CD4+ CD25highT细胞比例降低,外来抗原刺激后比例升高,但与健康正常人存在差异。这可能与其复杂的系统免疫学发病机制相关。     

Profiles of Foxp3+ regulatory T cells in eczematous dermatitis, psoriasis vulgaris and mycosis fungoides

Background It is well known that regulatory T cells (Tregs), identified by their expression of CD4, CD25 and Foxp3, play a crucial role in maintaining peripheral tolerance. Recently, it has been demonstrated that a Treg population resides in normal human skin. However, only a few studies have demonstrated the presence of Foxp3+ Tregs in inflammatory skin disorders. Objectives In this study, we immunohistologically examined the presence of CD4+ CD25+ Foxp3+ Tregs in the lesional skin of psoriasis vulgaris, mycosis fungoides and eczematous dermatitis. Methods We used immunohistochemistry to examine the presence of Foxp3+ Tregs in fixed sections of the lesional skin from 16 patients with psoriasis vulgaris, 17 patients with mycosis fungides and 18 patients with eczematous dermatitis in addition to 10 normal skin samples. Results In normal skin, epidermal and dermal Foxp3+ cells were rare. The psoriasis vulgaris, mycosis fungoides and eczematous dermatitis samples contained substantial numbers of epidermal and dermal CD3+, CD4+ and CD25+ Foxp3+ Tregs. The epidermis contained a higher percentage of CD3+, CD4+ and CD25+ Foxp3+ cells than the dermis. The percentage of Foxp3+ cells among CD3+ or CD4+ cells was significantly lower in eczematous dermatitis than in psoriasis vulgaris or mycosis fungoides, and that of dermal Foxp3+ cells was significantly lower in psoriasis vulgaris than in eczematous dermatitis or mycosis fungoides. Conclusions The lower percentage of epidermal or dermal Foxp3+ cells in eczematous dermatitis or psoriasis vulgaris, respectively, might contribute to their pathogenesis.     

CD1a+, CD3+, CD4+, CD8+, CD68+ and cutaneous lymphocyte-associated antigen-positive cells in Bowen's disease

BACKGROUND: Bowen's disease (BD) is a squamous cell carcinoma in situ that rarely invades into the underlying dermis. However, little is known about its immunohistology. Objectives To evaluate the relationship between the cytological properties of the tumour cells in BD and the host immune response. METHODS: We examined the expression of p53, proliferating cell nuclear antigen (PCNA) and Ki67 antigen, and the number of mitotic cells, together with the number of intratumoral and dermal infiltrating CD1a+, CD3+, CD4+, CD8+, CD68+ and cutaneous lymphocyte-associated antigen (CLA)+ cells in 18 cases of genital BD. RESULTS: When compared with normal genital skin (n = 10), there was a significantly higher number of mitotic cells as well as higher expression of p53+, PCNA+ and Ki67+ cells in BD. There was significant mutual correlation between CD3+, CD4+ and CD68+ cells in the tumoral epidermis. The number of CD1a+ Langerhans cells significantly decreased in BD epidermis; however, dermal CD1a+ cells were increased. Interestingly, numbers of dermal CD1a+ cells significantly correlated with those of intratumoral CD3+, CD4+ and CD68+ cells. In situ hybridization for human papillomavirus (HPV) demonstrated that HPV-infected BD had significantly less infiltration of intratumoral CD3+ cells and CLA+ cells. CONCLUSIONS: The present data suggest that dermal CD1a+ cells may participate in the immune surveillance and that HPV infection may interfere with the intratumoral infiltration of CLA+ cells in BD.