Increased frequency of intracellular interleukin (IL)-13 and IL-10, but not IL-4, expressing CD4+ and CD8+ peripheral T cells of patients with atopic dermatitis

BACKGROUND: A number of studies exist demonstrating the increased expression of type 2 cytokines and decreased capacity to produce interferon-gamma (IFN-gamma) in peripheral blood mononuclear cells (PBMCs) of patients with atopic dermatitis (AD). OBJECTIVES: To clarify the results of recent studies concerning the role of interleukin (IL)-4 and IL-13 in PBMCs of AD patients, we analysed the activation status of lymphocyte subpopulations. METHODS: We measured the intracellular expression and serum levels of certain type 1 and type 2 cytokines, using cell surface and intracellular cytokine staining, flow cytometry and enzyme-linked immunosorbent assay techniques. RESULTS: The frequency of IL-10 and IL-13 producing CD4+ and CD8+ T cells was significantly higher in patients with AD, while the frequency of IFN-gamma secreting helper and cytotoxic T cells was significantly lower in patients with AD than in control subjects. The serum levels of IL-10 and IL-13 were also significantly increased. There were no significant differences observed between the experimental groups in the frequency of IL-4 producing CD4+ and CD8+ cells. CONCLUSIONS: This study demonstrates a type 2 cytokine production in the CD4+ and CD8+ T cells of AD patients, which is characterized by an elevated IL-13, but not by IL-4 secretion, and by an increased level of the immunoregulatory IL-10, which can contribute to a decrease in IFN-gamma expression.     

Immunohistochemical studies on NAP-1/IL-8 in contact eczema and atopic dermatitis

Summary The neutrophil activating peptide NAP-1/IL-8 has in the past been shown to be secreted by diverse cell-types involved in inflammatory processes. Furthermore, potent biological effects on both neutrophilic granulocytes and lymphocytes enforce its role in inflammation. Recently, immunohistochemical studies using monoclonal anti-NAP-1/IL-8 antibodies have been performed on dermal inflammatory conditions like psoriasis vulgaris. These have demonstrated epidermal IL-8 immunoreactivity in a pattern inversely related to the degree of inflammatory infiltration. Based on these results, in the present study biopsies from patients with contact eczema as well as atopic dermatitis were examined. The same patterns of immunoreactivity were found with either homogenous epidermal staining, focally negative staining or overall decreased or even absent staining. As in psoriasis, these patterns were related to the degree of inflammatory infiltration. These results prove NAP-1/IL-8 to be involved not only in psoriasis vulgaris, but more likely to be a marker of different inflammatory processes. Future work will have to examine the kinetics as well as stimuli causing these effect.     

Decreased suppression of CD8+ and CD4+ T cells by peripheral regulatory T cells in generalized vitiligo due to reduced NFATC1 and FOXP3 proteins

Regulatory T cells (Tregs) are involved in the suppression of activated T cells in generalized vitiligo (GV). The study was aimed to investigate Tregs functional defects in Treg:CD8⁺ and Treg:CD4⁺ T cells' co-culture systems of 55 GV patients and 45 controls. CD8⁺ and CD4⁺ T-cell proliferation was assessed by BrdU assay; production of IL-10, TGF-β and IFN-γ cytokines was assessed by ELISA; and FOXP3, CD25, NFATC1 and CD44 proteins were measured by flow cytometry. Generalized vitiligo patients showed reduced suppression of CD8⁺ and CD4⁺ T cells (P = .0384, P = .0084), increased IFN-γ (P < .0001, P = .0019), decreased IL-10 and TGF-β (P < .0001) and decreased FOXP3, CD25 and NFATC1 proteins (P < .0001). Active vitiligo (AV) patients showed reduced suppression of CD8⁺ & CD4⁺ T cells (P = .006, P = .015), increased IFN-γ (P = .036, P = .045), decreased IL-10 (P = .009, P = .021), FOXP3 (P = .0244) and NFATC1 (P = .019). Severe GV (50%-75% VASI) patients showed reduced suppression of CD8⁺ and CD4⁺ T cells (P = .0003, P = .001), increased IFN-γ (P = .0029, P < .0001), decreased IL-10 (P = .0057, P = .0017), FOXP3 (P = .002) and NFATC1 (P = .0347). VASI score was positively correlated with the suppression of CD8⁺ and CD4⁺ T cells (P = .0006, P < .0001), IL-10 (P = .0096, P = .029), FOXP3 (P = .0008) and NFATC1 (P = .043), whereas it was negatively correlated with IFN-γ (P = .0029, P = .0017). Early age of onset patients' Tregs demonstrated decreased suppression of CD8⁺ and CD4⁺ T cells (P = .0156, P = .0074), decreased TGF-β (P = .0212, P = .0083) and NFATC1 (P = .0103). NFATC1 was positively correlated with FOXP3 in Tregs (P < .0001). Our results suggest impaired Tregs suppressive function in GV patients due to decreased NFATC1, FOXP3, CD25, IL-10 and TGF-β resulting into increased CD8⁺ and CD4⁺ T-cell proliferation and IFN-γ production. For the first time, decreased NFATC1 levels were correlated with decreased FOXP3, thereby altering Treg cell function in GV patients. Additionally, decreased Treg cell function also affected onset, activity and severity of GV.     

早期隐性梅毒对慢性HIV感染者CD4+T及CD8+T淋巴细胞内Caspase-1/3水平的影响

目的：明确早期隐性梅毒感染对HIV感染者CD4+T及CD8+T细胞Caspase-1/3水平的影响。方法：流式细胞仪检测18例早期隐性梅毒合并慢性HIV感染者（合并组）以及18例单纯慢性HIV感染者（HIV组）CD4+T及CD8+T细胞内Caspase-1(细胞焦亡标志物)和Caspase-3(细胞凋亡标志物)含量。驱梅治疗6个月后再检测合并组CD4+T及CD8+T细胞内Caspase-1/3含量,与治疗前进行比较。结果：与单纯HIV感染组比较,合并组CD4+T及CD8+T细胞中Caspase-1升高（均P＜0.05）,Caspase-3含量无统计学差异（均P＞0.05）。与治疗前比较,合并组驱梅治疗6个月后,CD4+T及CD8+T细胞中Caspase-3明显下降（均P＜0.05）,Caspase-1含量治疗前后无统计学差异（均P＞0.05）。结论：合并梅毒螺旋体感染可能影响HIV感染者CD4+T和CD8+T淋巴细胞的焦亡和凋亡。     

CD4+ T cells producing interleukin (IL)‐17, IL‐22 and interferon‐γ are major effector T cells in nickel allergy

Background It has been suggested that interleukin (IL)‐17 and IL‐22 play important roles in the elicitation of human allergic contact dermatitis; however, the frequencies of T cell subtypes producing IL‐17 and IL‐22 in human allergic contact dermatitis are unknown. Objectives To determine the frequencies of CD4⁺, CD8⁺ and γδ T cells producing IL‐17, IL‐22 and interferon (IFN)‐γ in the blood and skin from nickel‐allergic patients. Patients/materials/methods Blood samples were collected from 14 patients and 17 controls, and analysed by flow cytometry. Biopsies were taken from 5 patients and 6 controls, and analysed by immunohistochemistry and flow cytometry of skin lymphocytes. Results We found an increased frequency of γδ T cells in the blood, but no differences in the distribution of cytokine‐producing CLA⁺ T cell subtypes in nickel‐allergic patients as compared with controls. In nickel‐allergic patients, there was massive cellular infiltration dominated by CD4⁺ T cells producing IL‐17, IL‐22 and IFN‐γ in nickel‐challenged skin but not in vehicle‐challenged skin. Conclusion CD4⁺ T cells producing IL‐17, IL‐22 and IFN‐γ are important effector cells in the eczematous reactions of nickel‐induced allergic contact dermatitis in humans.     

Human T‐lymphotropic virus 1 (HTLV‐1)‐associated lichenoid dermatitis induced by CD8+ T cells in HTLV‐1 carrier,HTLV‐1‐associated myelopathy/tropical spastic paraparesis and adult T‐cell leukemia/lymphoma

Human T‐lymphotropic virus type 1 (HTLV‐1) induces adult T‐cell leukemia/lymphoma (ATLL), HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) and carrier. ATLL is a mature CD4⁺CD25⁺CCR4⁺ T‐cell neoplasm, and approximately half of patients have direct skin involvement manifesting patch, plaque, tumor, multiple papules, erythroderma and purpura. However, there exist secondary eruptions without tumor cell infiltration in patients with ATLL or HAM/TSP and carriers of HTLV‐1. To clarify the presence of reactive skin eruptions in HTLV‐1‐infected individuals, we reviewed our patients with HTLV‐1‐associated diseases. In 2002–2012, we saw 50 ATLL or HAM/TSP patients and HTLV‐1 carriers presenting with skin lesions. We retrospectively selected cases that histologically showed lichenoid tissue reactions with predominant infiltration of CD8⁺ T cells, but not CD4⁺ tumor cells. The cases included erythroderma (HTLV‐1 carrier), lichen planus (HTLV‐1 carrier), alopecia areata (HAM/TSP), chronic actinic dermatitis (HTLV‐1 carrier to acute ATLL conversion) and discoid lupus erythematosus (smoldering ATLL). They were graft‐versus‐host disease‐like, major secondary lesions and seen in HTLV‐1 carriers and patients with HAM/TSP and smoldering ATLL. We coin the term HTLV‐1‐associated lichenoid dermatitis (HALD) to encompass the conditions. HALD may occur in association with the elevated immunity toward HTLV‐1‐infected CD4⁺ T cells, thus sharing the pathogenetic role of cytotoxic T cells with HAM/TSP.