Possible role of superantigens in inducing autoimmunity in pemphigus patients

The diagnostic and pathological relevance of anti‐desmoglein autoantibodies in common forms of pemphigus has been well established, and T cells have been shown to play a role in the onset and progression of these diseases. The role of superantigens in provoking polyclonal activation of T cells with many different fine specificities, possibly including autoreactive T cells and T‐cell mediated autoantibody response, is unknown. Further, abnormal T‐cell function may lead to opportunistic infections particularly with Candida. The response of T cells of pemphigus patients to recall antigens of these opportunists is not clear. The aim of this study was to investigate the in vitro response of T lymphocytes from pemphigus patients to common bacterial superantigens such as streptococcal pyrogenic exotoxin A and staphylococcal enterotoxin B, and recall antigens such as Candida antigen. Changes in CD3⁺CD4⁺ and CD3⁺CD8⁺ T‐cell sub‐populations and expression of naive/memory markers (CD45RA⁺/RO⁺) on different T cells were analyzed by flow cytometry. Significant elevation in CD3⁺CD4⁺ and expression of the memory (CD45RO⁺) markers on these cells was observed both in pemphigus vulgaris and pemphigus foliaceus patients, as compared to healthy controls, upon stimulation with streptococcal pyrogenic exotoxin A and staphylococcal enterotoxin B. However, only memory T cells (CD45RO⁺) were significantly increased upon Candida antigen stimulation. Our study suggests that CD4⁺ memory T lymphocytes may modulate the pathogenic autoantibody response in pemphigus patients, and also emphasizes the possibility that the superantigen‐reactive T cells participate in the triggering of autoimmunity in pemphigus.     

Evaluation of activatory and inhibitory natural killer cell receptors in non-segmental vitiligo: a flow cytometric study

Background Recent observations established the role of altered cellular immunity and autoimmune hypothesis in the pathogenesis of vitiligo. There have been several reports discussing T‐cell and natural killer (NK) cell populations, but NK cell receptors were not evaluated in vitiligo. Objective The purpose of this investigation was to assess the role of T and NK cells as well as activatory and inhibitory NK cell receptor alterations in the pathogenesis of vitiligo and whether any aberrations were correlated with clinical findings of the disease. Patients/methods Fifty‐three patients with non‐segmental vitiligo and 45 age‐ and sex‐matched healthy controls were enrolled in the study. The percentages of lymphocytes, granulocytes, monocytes and CD3, CD4, CD8, CD14, CD16, CD56, CD45, CD45RA, CD54RO, CD28, CD80, CD94, CD158a, KIR3DL‐1 receptors as well as CD94, CD158a, KIR3DL‐1 receptors on CD16⁺ cells were detected by using flow cytometry. The patient and control groups were compared in terms of the results of flow cytometric analysis, and the results were assessed regarding the type and activity of vitiligo. Results The percentages of CD16⁺CD56⁺, CD3⁺CD16⁺CD56⁺, CD8⁺ and CD45RO⁺ cells were significantly increased in vitiligo group compared with the controls. No difference was detected between the patients and control groups in percentages of CD3⁺, CD4⁺, CD3^?CD16⁺CD56⁺, CD28⁺, CD45⁺, CD45RA⁺, CD94⁺, CD158a⁺ and KIR3DL‐1⁺ cells. The percentage of CD16⁺CD158a⁺ cells was significantly decreased in a randomized selected group of vitiligo patients. There were no differences in percentage expression of studied cell surface antigens between patients in the active or stable period. CD3⁺ cells were significantly increased in generalized form, and CD45RO⁺ cells were significantly increased in acral/acrofacial form when compared with the other types of vitiligo. Conclusions These results indicate further evidence for T and NK cell abnormalities in non‐segmental vitiligo. The present data show that NK cell activation may be responsible in the pathogenesis of vitiligo in conformity with decreased inhibitory and increased activatory NK cell receptors.     

Differential distribution of haematopoietic and nonhaematopoietic progenitor cells in intralesional and extralesional keloid: do keloid scars provide a niche for nonhaematopoietic mesenchymal stem cells?

Background Keloid disease is a benign, quasineoplastic disease with a high recurrence rate. Mesenchymal‐like stem cells (MLSC) have previously been demonstrated in keloid scars and may be involved in keloid pathobiology. However, as these cells have only been examined by single colour fluorescence activated cell sorting (FACS) alone, they need to be more comprehensively characterized so that the key cellular contributors to keloid scars can be better understood. Objectives To identify and characterize MLSC in intralesional and extralesional keloid, and to distinguish haematopoietic stem cells (HSC) from mesenchymal stem cells (MSC). Methods and patients Punch biopsies from intralesional (top, middle and margin) and extralesional keloid scar sites were obtained from 17 patients with a keloid. Multicolour FACS analysis using antibodies specific for HSC markers CD34 and CD117 and MSC markers CD13, CD29, CD44 and CD90 was performed on freshly isolated keloid scar cells and on passage 0 and 1 cells. This was complemented by real‐time quantitative polymerase chain reaction (PCR) and immunohistological in situ analyses. Results Keloid scars contain distinct subpopulations of MLSCs. Cells positive for CD13, CD29, CD44 and CD90 were found to be significantly (P < 0·05) higher in the top and middle compartments of keloid scars compared with extralesional skin, where cells positive for CD34, CD90 and CD117 (representing HSCs) predominated. A unique population of CD34+ cells (cells positive for CD13, CD29, CD34, CD44 and CD90) were found in keloid scars and in extralesional skin. FACS and quantitative PCR analysis showed that many of the MSC markers were progressively downregulated and all HSC markers were lost during extended keloid fibroblast culture up to passage 1. Conclusion We have found distinct subpopulations of haematopoietic and nonhaematopoietic MSC in keloid scars, whereby HSC accumulate extralesionally, while keloids seem to provide a niche environment for nonhaematopoietic MSC. Future therapy of keloids may have to target differentially both stem cell populations in order to deprive these tumours of their regenerative cell pools.     

Perturbations of both nonregulatory and regulatory FOXP3+ T cells in patients with malignant melanoma

Background ‘FOXP3+ regulatory T cells’ (Tregs) are reported to be increased in tumour‐bearing hosts including patients with melanoma, leading to tumour immune suppression. However, this idea is challenged by recent evidence that the ‘FOXP3+ Treg’ fraction in fact contains activated ‘nonregulatory’ T cells. Also, FOXP3+ T cells are reported to have functionally and kinetically distinct subsets. Objectives To investigate whether either or both of regulatory and ‘nonregulatory’ FOXP3+ T cells are perturbed in patients with melanoma. Methods FOXP3+ T cells were classified into three subsets, namely CD45RO+FOXP3^low nonregulatory T cells, CD45RO+FOXP3^high effector Tregs, and CD45RO?FOXP3^low naïve Tregs, according to their expression levels of FOXP3 and CD45RO. The percentage and cytokine production of these FOXP3+ T‐cell subsets were assessed by flow cytometry. Results Both regulatory and nonregulatory T cells were increased in patients with melanoma. Moreover, we found three unexpected perturbations in FOXP3+ T‐cell subsets: (i) patients with melanoma showed higher frequencies of FOXP3^low nonregulatory T cells, which decreased and normalized after tumour removal; (ii) FOXP3^low naïve Tregs containing higher frequencies of interferon‐γ+ cells increased with tumour progression; and (iii) CD45RO+FOXP3^high effector Tregs were pronouncedly infiltrated around tumour tissues. Conclusions These findings demonstrate that patients with melanoma have distinct and differential perturbation of both regulatory and nonregulatory FOXP3+ T cells. The degree of perturbation is associated with tumour burden and progression, suggesting that the perturbation reflects fundamental pathophysiological processes in patients with melanoma. The presented analysis provides a practical approach to investigate the immunological environment of cancer patients.     

Detection of CD4+ CD25+ FOXP3+ regulatory T cells in peripheral blood of patients with chronic autoimmune urticaria

Background/Objectives: Compelling evidence indicates a significant role for a population of CD4⁺ T regulatory cells in suppressing immune responses and in maintaining immunological homeostasis. This study aims to investigate the potential role of CD4⁺CD25^HIGHFOXP3⁺ T regulatory cells in patients with chronic autoimmune urticaria and to define the characteristics of CD4⁺CD25^HIGHFOXP3⁺ cells in chronic urticaria. Methods: We used flow cytometry to assess the expression of CD4⁺CD25^HIGHFOXP3⁺ cells in the peripheral blood mononuclear cells of patients with chronic autoimmune urticaria. Results: In this study, we found that patients with chronic autoimmune urticaria have a significantly reduced frequency of CD4⁺CD25^HIGHFOXP3⁺ cells (1.39 ± 0.27% vs 2.09 ± 0.34%; P = 0.001) in their peripheral blood, accompanied by a decreased intensity of FOXP3 expression (50.13 ± 9.79 vs 68.19 ± 6.40; P < 0.001). Notably, although patients with chronic idiopathic urticaria had a reduced frequency of CD4⁺CD25^HIGHFOXP3⁺ cells (1.85 ± 0.46% vs 3.64 ± 0.48%; P < 0.001), their FOXP3 expression levels did not differ from those in healthy controls. Conclusions: Patients with chronic autoimmune urticaria displayed a reduced percentage of CD4⁺CD25⁺FOXP3⁺ regulatory T cells. The results imply CD4⁺CD25⁺FOXP3⁺ regulatory T cells may contribute to the autoimmune pathological process of chronic autoimmune urticaria.     

Expression of CD30 on T helper cells in the inflammatory infiltrate of acute atopic dermatitis but not of allergic contact dermatitis

Abstract  The CD30 molecule has been proposed as a marker for a subset of CD4⁺CD45RO⁺ (memory) T cells with potent B cell helper activity producing IL-5 and IFN-γ and as a specific marker for Th2 cells. Recently, an association has been demonstrated between elevated serum levels of soluble CD30, which is shed by CD30⁺ cells in vitro and in vivo, and atopic dermatitis but not respiratory atopic disorders or allergic contact dermatitis. We studied the expression of CD30 in the inflammatory infiltrate of atopic dermatitis compared with that of allergic contact dermatitis, with special regard to skin disease activity (acute vs subacute/ chronic). Biopsies were obtained from 16 patients suffering from atopic dermatitis (acute n = 6, subacute/ chronic n = 10), from 7 patients with acute allergic contact dermatitis and from 5 positive patch-test reactions. Paraffin-embedded as well as snap-frozen material was stained with anti-CD30 and anti-CD45RO mAbs according to standard procedures. Double-staining procedures for CD30CD3, CD30CD4, CD30CD45RO and CD30CD68 were also performed. Abundant CD45RO⁺ cells were detected both in atopic dermatitis and in allergic contact dermatitis lesions. We found scattered CD30⁺ cells in only one of six formalin-fixed paraffin-embedded acute atopic dermatitis biopsies, but in all of the respective snap-frozen specimens, possibly because CD30 expression on atopic dermatitis infiltrating cells is weak and sensitive to formalin fixation and paraffin embedding. CD30CD3 and CD30CD4 double staining identified CD30⁺ cells to be helper T lymphocytes. No significant CD30 expression (either in paraffin-embedded or in frozen material) could be found in subacute/chronic atopic dermatitis lesions or in any of the specimens of allergic contact dermatitis. The results suggest a specific regulatory function of CD30⁺ T cells in acute atopic dermatitis. With respect to the view that CD30 is a marker for Th2 cells, our observations confirm previous findings that Th2 cells predominate in the infiltrate particularly of acute atopic dermatitis. CD30 expression in acute atopic dermatitis but not in acute allergic contact dermatitis might be helpful in the histological differentiation of these disorders and in the further characterization of atopy patch testing. Received: 1 April 1998 / Received after revision: 28 May 1998 / Accepted: 3 July 1998     

Identification of fibrocytes from mesenchymal stem cells in keloid tissue: a potential source of abnormal fibroblasts in keloid scarring

Abnormal fibroblasts have been implicated in keloid formation, a benign but fibroproliferative skin disorder. However, the exact source of these cells remains unknown. Fibrocytes are considered to be hybrid mesenchymal/hematopoietic cells, having been identified in various fibrotic disorders as the precursors of fibroblasts. Therefore, we hypothesized that a population of fibrocytes is present in keloid tissue as opposed to the mesenchymal stem cells (MSCs). We compared the proportion of MSCs in keloid versus bone marrow-derived cells and compared fibrocytes in keloid as opposed to normal scar tissue. We also investigated the propagation of fibrocytes in serum-supplemented versus serum-free media. Using multicolor fluorescence-activated cell analysis, we found distinct populations of MSCs (CD34(-)CD73(+)CD90(+)CD105(+)) that were different from CD45RO(+)25F9(+)MRP8/14(+) fibrocytes present in keloid tissue, while very few fibrocytes were observed in normal scar tissue. The proportion of keloid-derived cells in serum-free or serum-supplemented cultures expressing these fibrocyte markers was greater than from cultures derived from normal scar tissue (p?相似文献   

Coexpression of CCR6 and CD146 (MCAM) is a marker of effector memory T-helper 17 cells

Effector memory T (T_EM) cells are a subpopulation of memory T cells that express receptors mediating migration to inflamed tissues and produce various cytokines. Effector memory T‐helper (Th)17 (Th17_EM) cells are thought to be essential for inflammation in Th17‐mediated diseases, but have not been studied in detail. To identify superior surface markers to isolate a homogeneous population of Th17_EM cells from peripheral blood, CD4⁺ T cells were isolated from the peripheral blood of healthy donors based on the expression of CCR7, CCR6 and CD146 using six‐color flow cytometry. After 4 days of culture in the presence of anti‐CD3/28 beads, intracellular cytokines were determined by flow cytometric analysis. To investigate the relevance of Th17_EM cells in Th17‐mediated disease, the frequencies of T_EM‐cell subsets in psoriasis were quantified using six‐color flow cytometry. An enzyme‐linked immunosorbent assay was performed to confirm the interleukin (IL)‐17‐producing capacity of T_EM‐cell subsets from the peripheral blood of a patient with psoriasis. CCR6⁺CD146⁺ T_EM (CD4⁺CD45RA^?CCR7^?) cells had a greater capacity to produce IL‐17 than CCR6⁺CD146^? or CCR6^?CD146⁺ T_EM cells. Although the percentage of CCR6⁺CD146⁺ cells in T_EM cells was not significantly different between patients with psoriasis and controls, three of eight patients had a higher percentage of CCR6⁺CD146⁺ T_EM cells than the mean +5 standard deviations of the controls. Coexpression of CCR6 and CD146 is a useful marker for Th17_EM cells. Increasing the number of CCR6⁺CD146⁺ Th17_EM cells in peripheral blood may facilitate estimation of systemic Th17‐cell activity in Th17‐mediated diseases.     

Introduction

Psoriasis is an immune-mediated skin disease in which T cells initiate and maintain the pathogenic process.1 T cells become activated, migrate into the skin, and induce the keratinocyte proliferation associated with the psoriatic phenotype. The activated T cells that infiltrate the skin express the memory phenotype (CD45RO⁺).2,3 Both CD4⁺ and CD8⁺ memory T-cell subtypes are believed to play a role in the pathogenesis of psoriasis. The effectiveness of many traditional therapies for psoriasis (e.g., cyclosporine, methotrexate, psoralen/ultraviolet A light) can be attributed, at least in part, to the potent immunosuppressive effects of these treatments.4,5 Unfortunately, a lack of selective targeting of the immune system by these therapies may result in treatment-limiting side effects.     

Expression of T‐cell immunoglobulin and immunoreceptor tyrosine‐based inhibitory motif domain on CD4+ T cells in patients with atopic dermatitis

The T‐cell immunoglobulin and immunoreceptor tyrosine‐based inhibitory motif domain (TIGIT) is a co‐inhibitory receptor mainly expressed on T cells. Although TIGIT plays an important role in various autoimmune diseases, its role in atopic dermatitis (AD) remains unclear. In this study, we examined the expression levels of TIGIT and their association with clinical features in patients with AD. TIGIT expression on CD4⁺ T cells, central memory T cells, effector memory T cells and regulatory T cells was determined by flow cytometry. CD4⁺ T cells exhibited enhanced TIGIT expression in patients with AD compared with healthy individuals. In particular, effector memory T cells and regulatory T cells, but not central memory T cells, exhibited higher TIGIT expression in patients with AD than in healthy individuals. The frequency of TIGIT⁺ cells among CD4⁺ T cells was significantly increased in patients with mild AD compared with healthy individuals, while decreased in patients with severe AD. Consistently, the frequency of TIGIT⁺ cells among CD4⁺ T cells was negatively correlated with both serum thymus and activation‐regulated chemokine levels and immunoglobulin E levels in patients with AD. Furthermore, TIGIT expression on CD4⁺ T cells inhibited cell proliferation in patients with AD. These results suggest that TIGIT expression on CD4⁺ T cells in patients with AD may be increased to suppress chronic cutaneous inflammation. Moreover, TIGIT expression may be impaired in a subset of patients with AD, leading to a deterioration of skin inflammation. Our study may provide new insight into a TIGIT pathway‐based therapeutic approach for AD.     

The role of stem cell factor and c‐KIT in keloid pathogenesis: do tyrosine kinase inhibitors have a potential therapeutic role?

Background Keloids are fibroproliferative disorders characterized by increased deposition of extracellular matrix components. Stem cell factor (SCF) and its receptor c‐KIT are expressed in a wide variety of cells and have also been demonstrated to be important modulators of the wound healing process. Objectives To examine the role of the SCF/c‐KIT system in keloid pathogenesis. Methods Immunohistochemical staining and Western blot analyses were used to examine localization and expression of SCF and c‐KIT in keloid and normal skin tissue. This was followed by the detection of SCF and c‐KIT expression in fibroblasts cultured in vitro and fibroblasts exposed to serum. To investigate the effect of epithelial–mesenchymal interactions, a two‐chamber system was employed in which keratinocytes on membrane inserts were cocultured with the fibroblasts. SCF and c‐KIT expression levels in all cell extracts and conditioned media were assayed by Western blotting. In another set of experiments, the effect of imatinib (Glivec^®, Gleevec^®; Novartis Pharma AG, Basel, Switzerland) on keloid fibroblasts was examined. Results SCF and c‐KIT were upregulated in keloid scar tissue and in cultured fibroblasts stimulated with serum, highlighting their importance in the initial phase of wound healing. We further demonstrated that epithelial–mesenchymal interactions, mimicked by coculture of keratinocytes and fibroblasts in vitro, not only stimulated secretion of the soluble form of SCF in keloid cocultures but also brought about shedding of the extracellular domain of c‐KIT perhaps by upregulation of tumour necrosis factor‐α converting enzyme which was also upregulated in keloid scars in vivo and keloid cocultures in vitro. In addition keloid cocultures expressed increased levels of phosphorylated c‐KIT highlighting an activation of the SCF/c‐KIT system. Finally, we demonstrated that imatinib, a tyrosine kinase inhibitor, may be a possible therapeutic agent for keloids. Conclusion These data indicate that the SCF/c‐KIT system plays an important role in scar pathogenesis, and underscore the role of imatinib as a key therapeutic agent in keloid scars.     

Inverse correlation between CD34 expression and proline-4-hydroxyase immunoreactivity on spindle cells noted in hypertrophic scars and keloids

The CD34 positive (CD34+) spindle cells constitute a special population of spindle cells which show a unique distribution in the skin. So far, however, the functional role of CD34+ spindle cells and the regulation of CD34 expression on dermal spindle cells are totally unknown. We examined immunohistologically the pattern of the expression of CD34 and proline-4-hydroxylase, a marker for the fibroblasts that participate in active collagen synthesis, on dermal spindle cells at various stages of scar and keloidal tissues.
Dermal spindle cells in the lesions of hypertrophic scar and those at inflammatory expanding borders of keloids totally lost CD34 expression, but they strongly expressed proline-4-hydroxylase. On the other hand, they expressed CD34, together with decreased immunoreactivity to anti-proline-4-hydroxylase antibody, in non-inflammatory scars or in a non-inflammatory central portion of keloid. In two cases of scars, in which inflammation began to subside, double immunofluorescence demonstrated that both CD 34 and proline-4-hydroxylase were expressed on the same spindle cells.
CD34 expression, once disappeared from the lesions of hypertrophic scar or keloid, seems to return on CD34–proline-4-hydroxylase+ cells, when the initial inflammatory changes begin to regress. There is a reverse correlation between CD34 expression on spindle cells and the synthesis of type I collagen in the skin.     

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.     

Role of macrophage infiltration in successful repigmentation in a new periphery‐spreading vitiligo lesion in a male Japanese patient

Vitiligo is an acquired disorder in which depigmented macules result from mostly autoimmune loss of melanocytes. The initiating process in vitiligo has still been uncertain. Here, we report the case of a 19‐year‐old man with undetermined/unclassified vitiligo with a new periphery‐spreading vitiligo lesion on the right dorsal hand after rigorous sun exposure. Histopathological evaluation showed noticeable infiltration of CD68⁺ macrophages, moderate infiltration of CD3⁺ T cells, little infiltration of CD8⁺ T cells and CD11c⁺ myeloid dendritic cells, HMB45/CD11c double‐positive cells, and Melan‐A/MART1⁺ deposits in the dermis. We surmised that melanocyte‐derived deposits were mostly phagocytosed by CD68⁺ macrophages and were faintly phagocytosed by CD11c⁺ myeloid dendritic cells, referring distribution of CD68⁺ mononuclear cells and melanocyte biomarkers. Complete repigmentation was achieved following topical application of hydrocortisone butyrate propionate 0.1% ointment. We summarize that prompt clearance of debris by macrophages would be essential to an excellent prognosis of complete repigmentation.     

Increased expression of PD1 and CD39 on CD3+CD4+ skin T cells in the elderly

Normal ageing is associated with an impaired systemic immune response contributing to an increased susceptibility to infectious diseases. The aim of this study was to compare the lymphocyte phenotype in human skin from old and young healthy subjects. Skin samples from donors were used for explant cultures before flow cytometric analysis. Our results depicted a higher proportion of CD4⁺ and a lower proportion of CD8⁺ among CD3⁺ T cells, a decreased proportion of CD45RA⁺ naive T cells (3.5 ± 1.9% vs 22.9 ± 11.1%, P ≤ 0.007) and an upregulation of the expression of CD39 and PD1 on CD3⁺CD4⁺ T cells (25.1 ± 8.5% vs 12.5 ± 8.5%, P ≤ 0.003, 68.8 ± 11.6% vs 50.0 ± 11.3%, P ≤ 0.01, respectively) in the skin of old subjects. These findings could explain a reduced generation of long‐lived memory T cells and an impaired antitumoral response in the skin of the elderly.     

Regulation of nickel-induced T-cell responsiveness by CD4+CD25+ cells in contact allergic patients and healthy individuals

In this study, we investigated the capacity of CD4⁺CD25⁺ regulatory T cells to suppress nickel‐specific effector T cells, both in nickel‐allergic patients and healthy controls. CD4⁺ cells isolated from allergic patients showed an increased proliferative response to nickel, whereas CD4⁺ cells from negative controls did not respond to allergen. When CD4⁺CD25⁺ cells were depleted, nickel‐specific responsiveness was strongly increased both in allergic and in non‐allergic individuals, with the most pronounced effect in allergic patients. These regulatory T cells were anergic to nickel but inhibited nickel‐specific CD4⁺CD25^– effector T cells in coculture experiments. CD4⁺CD25⁺ cells from nickel‐allergic patients showed only a limited capacity to suppress effector T‐cell responsiveness, because an increased nickel reactivity could still be detected in these cocultures. None of the isolated CD4⁺CD25⁺ cells, either isolated from healthy controls or allergic patients, produced IL‐10 in response to nickel. Overall, these results support the view that CD4⁺CD25⁺ cells can control the activation of nickel‐specific effector T cells in non‐allergic individuals, whereas this regulatory capacity is impaired in allergic patients. To investigate the presence of allergen‐specific regulatory T cells in truly naïve, non‐sensitized individuals, T‐cell reactivity should also be studied with non‐environmental contact allergens, such as para‐phenylenediamine.     

Characterization of the T cell response in allergic contact dermatitis caused by corticosteroids

Background Delayed allergic hypersensitivity reactions have classically been described as type IV reactions, which are caused by T cells; however, the respective roles of CD4⁺ and CD8⁺ cells are yet to be defined. A central role for CD8⁺ cytotoxic T cells as effector cells has been suggested. Objectives To determine the type of T cell involved in corticosteroid allergy. Methods We analysed the kinetics of T cell recruitment and the cytokine production profile in positive patch tests of 27 corticosteroid‐sensitized patients, as compared with control sites and control subjects. Skin biopsies, collected at 8, 24 and 48 hr following drug application, were embedded in paraffin for histological and immunohistological staining, and, in some cases, also deep‐frozen for gene expression analyses. Results CD3⁺ T cells were rapidly recruited in concert with the positivity of the patch test sites. High levels of interleukin (IL)‐4, IL‐5 and, to a lesser extent, interferon‐γ suggested that both Th2 and Th1 cytokines were implicated. IL‐4 was also produced by γδ T cell receptor (TCR) lymphocytes. Conclusions This study showed that, in allergic contact dermatitis caused by corticosteroids, the inflammatory infiltrate is composed of CD3⁺ T cells with a predominant Th2 cytokine profile, among which IL‐4 is also produced by γδ TCR lymphocytes.     

Evaluation of botulinum toxin type A for treating post burn hypertrophic scars and keloid in children: An intra-patient randomized controlled study

Background

Consequently, the management of post burn hypertrophic scars and keloid in children are a great challenge for the physicians, parents, and children themselves.

Purpose of the Study

To assess the efficacy and safety of treating hypertrophic and keloid scars with botulinum toxins injections.

Patients and Methods

This is a randomized intra-patient comparative study was conducted on 15 children with post burn hypertrophic and keloid scars. Children were randomized to receive Intralesional injection of botulinum toxins on one part of the hypertrophic scar/keloid where the other part was left as a control. The assessment of clinical improvement was measured by the Vancouver scar scale (VSS) and by skin analysis camera system. Sessions were performed every month for 6 months.

Results

Clinical and statistical dramatic improvement in the vascularity, pliability, and height of the lesions which have been injected with neuronox. Evaluation of the lesions by the Antera camera has proven marked changes in the vascularity and height. There was no correlations between Vancouver score improvement and variables such as the age, sex, skin type, and duration and lesion type.

Conclusions

The botulinum toxins proved its efficacy and safety in treatment of hypertrophic scars and keloid in children. It improved the associated itching and pain. Moreover it improves the pliability, erythema, and thickness of the scars.