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.     

Perforin and granzyme B expression in oral and cutaneous lichen planus - a comparative study

Background: Although cutaneous and oral lichen planus (LP) share similar histopathological features, oral LP often follows a recalcitrant course while LP skin lesions tend to be self‐limiting. Apoptosis, mediated by cytotoxic T‐cells in LP, may be triggered by the release of molecules such as perforin and granzyme B. As variation in clinical behavior can reflect differences in LP immune expression, we studied the role of those cytotoxic molecules in oral and cutaneous LP. Methods: We analyzed 16 cases of cutaneous LP and 29 of oral LP. The sections were studied on hematoxylin and eosin, CD4, CD8, perforin and granzyme B staining. Results: The mean number of immunostained cells expressing each cytotoxic molecule was significantly higher in oral LP than in cutaneous LP. A higher number of single necrotic keratinocytes (apoptotic bodies) was found in oral LP lesions when compared to cutaneous LP. Only in oral LP lesions, a higher number of CD4‐positive cells was found in active lesions when compared to regressive lesions. Conclusions: Our results confirm increased expression of granzyme B and perforin in oral LP lesions as compared to cutaneous LP. The increased expression suggests a relationship with the clinical behavior of the disease. Lage D, Pimentel VN, Soares TCB, Souza EM, Metze K, Cintra ML. Perforin and granzyme B expression in oral and cutaneous lichen planus – a comparative study.     

Perforin expression is upregulated in the epidermis of psoriatic lesions

BACKGROUND: There are currently very few data regarding the role of cell-mediated cytotoxicity in psoriasis. Both cytotoxic T lymphocytes and natural killer (NK) cells mediate cytotoxicity reactions, mainly by two distinct pathways, the perforin/granzyme and the Fas/Fas ligand pathway. OBJECTIVES: To study the expression and distribution of perforin, T- and NK-cell subsets in psoriatic lesional and nonlesional skin. METHODS: Skin biopsy specimens from both lesional and nonlesional skin of 11 patients with chronic plaque psoriasis and eight healthy controls were analysed by immunohistochemistry. RESULTS: We found a significant increase in CD4+ and CD8+ cells in psoriatic lesions compared with nonlesional and healthy skin. The expression of CD16+ NK cells was significantly lower in lesions compared with healthy skin. Perforin expression was significantly enhanced in the epidermis of psoriatic lesions. CONCLUSIONS: Perforin expression is upregulated in the epidermis of psoriatic lesions, suggesting a potential role for perforin in the creation of the psoriatic plaque.     

Dendritic cells and pattern of cytokines in paracoccidioidomycosis skin lesions

We demonstrated and quantified by immunohistochemistry epidermal Langerhans cells, CD34+ dermal dendrocytes (DDs), and cells expressing TNFalpha, interferon-gamma (IFNgamma), IL-5, and IL-10 in skin lesions of paracoccidioidomycosis (PCM). Sixty-one biopsies were classified in three groups according to the pattern of tissue response: Group 1, well-organized granuloma; Group 2, poorly organized granuloma; and Group 3, both kinds of granuloma. Langerhans cells had short and irregular dendrites in all groups and were decreased in number in Groups 1 and 2. CD34+ DDs did not differ in number from the control group. Group 1 was characterized by many cells expressing IFNgamma. Groups 2 and 3 exhibited large numbers of cells expressing IL-5 and IL-10. The data obtained suggest that well-organized granulomas reflect a better cellular immune response, and the large number of cells expressing IL-5 and IL-10 in Group 2 indicate an ineffective response in PCM skin lesions. Both kinds of granuloma in the same cutaneous lesion probably represent an intermediate response between the anergic and hyperergic poles. Group 3 also showed higher numbers of cells expressing TNFalpha when compared with the control group. Some cells expressing TNFalpha were dendritic and localized around the granuloma similar to the factor XIIIa+ DD localization that we previously described.     

Detection of perforin and granzyme B mRNA expressing cells in lichen sclerosus

Granzyme B and perforin messenger RNA (mRNA) expression has been shown to be a specific in vivo activation marker for cytotoxic cells. The aim of this study was to assess the contribution of cell-mediated cytotoxicity in the pathogenesis of lichen sclerosus. In situ hybridization and immunohistochemistry were performed on serial tissue sections of lesional skin biopsies and normal skin as control. Immunohistochemical staining showed that the cellular infiltrate of diseased skin consisted predominantly of T cells (CD3+) and some B cells (CD20+). Among T cells CD4+ and CD8+ cells were found in about equal numbers. In normal skin samples perforin and granzyme B mRNA expressing cells were only rarely found. In contrast, in biopsies from diseased skin a high percentage of infiltrating cells expressed mRNA for perforin and granzyme B. The perforin and granzyme B expressing cells were found in the dermal infiltrate and intraepidermally in close proximity to keratinocytes suggesting in situ activation of these cells. These findings provide evidence that cell-mediated cytotoxicity plays a significant role in tissue destruction in lichen sclerosus.     

The role of perforin-mediated apoptosis in lichen planus lesions

Lichen planus is recognized as a T-cell-mediated disease. Histologically, it is characterized by the formation of colloid bodies representing apoptotic keratinocytes. The apoptotic process mediated by CD8⁺ cytotoxic T lymphocytes (CTLs) and NK cells mainly involves two distinct pathways: the perforin/granzyme pathway and the Fas/FasL pathway. So far, little is known regarding the role of perforin-mediated apoptosis in lichen planus. In the present study, the expression and distribution of perforin, T and NK cell subsets in the epidermis and dermis of lesional and nonlesional lichen planus skin were studied. Skin biopsy specimens from lesional and nonlesional skin of ten patients with lichen planus and eight healthy persons were analysed by immunohistochemistry. Significant accumulation of T cells, particularly of CD4⁺ and CD8⁺ subsets, was found in both epidermis and dermis of lichen planus lesions compared with nonlesional and healthy skin. There were no significant differences in the incidence of NK cells (CD16⁺ and CD56⁺) between lesional, nonlesional and healthy skin. Perforin expression was significantly upregulated in the epidermis of lichen planus lesions. In conclusion, accumulation of perforin⁺ cells in the epidermis of lichen planus lesions suggest a potential role of perforin in the apoptosis of basal keratinocytes.     

Primary cutaneous CD8+ cytotoxic T‐cell lymphoma involving the epidermis and subcutis in a young child

CD8+ cytotoxic T‐cell lymphoma involving the skin represents a heterogeneous group of diseases that include subcutaneous panniculitis‐like T‐cell lymphoma, primary cutaneous aggressive epidermotropic CD8+ cytotoxic T‐cell lymphoma, and ‘type D’ lymphomatoid papulosis. In this report, we describe a case of CD8+ cytotoxic T‐cell lymphoma involving both the epidermis and subcutis. The patient was a 6‐year‐old girl who presented with a 3‐year history of multiple plaques on her trunk and legs. The lesions had relapsed twice but responded well to prednisone. Histopathologic examination showed the proliferation of atypical lymphocytes in the epidermis, dermis and subcutaneous tissue. On immunohistochemical analysis, the atypical lymphocytes were positive for βF1, CD3, CD8, perforin, granzyme B and TIA‐1, but negative for T‐cell receptor (TCR) γ, CD4, CD30 and CD56. It was difficult to classify this tumor in terms of the known types of cutaneous lymphoma, and this case should be differentiated with subcutaneous panniculitis‐like T‐cell lymphoma and primary cutaneous aggressive epidermotropic CD8+ T‐cell lymphoma.     

CD8~+T细胞对白癜风患者黑素细胞的杀伤机制

目的:明确CD8~+T细胞对白癜风患者黑素细胞的杀伤机制。方法:分选白癜风患者及正常人外周血CD8~+T细胞,分别与原代黑素细胞及永生化正常黑素细胞系PIG1及永生化白癜风黑素细胞系PIG3V建立共孵育杀伤模型,采用流式细胞术检测靶细胞被杀伤情况,酶联免疫吸附法(ELISA)检测杀伤环境中IFN-γ、TNF-α、颗粒酶B及穿孔素的分泌水平。结果:白癜风患者外周血CD8~+T细胞杀伤原代黑素细胞及PIG3V能力,分泌IFN-γ、颗粒酶B及穿孔素水平均高于健康对照,而杀伤PIG1能力和TNF-α水平并无显著差异;白癜风患者CD8~+T细胞IFN-γ分泌水平与细胞杀伤率呈明显正相关。结论:白癜风患者CD8~+T细胞杀伤黑素细胞是白癜风发病的重要机制,且该杀伤作用可能依赖IFN-γ、颗粒酶B及穿孔素分泌水平的上调。     

T helper type 2-biased natural killer cell phenotype in patients with pemphigus vulgaris

Pemphigus vulgaris (PV) is an autoantibody-mediated bullous disease, but the role of natural killer (NK) cells in its pathogenic process has never been examined in detail. Circulating CD56+ CD3- NK cells as well as CD69+-activated NK cells were increased in PV patients compared with healthy controls and patients with other autoantibody-mediated autoimmune diseases, including immune thrombocytopenic purpura and myasthenia gravis. Gene expression analysis of highly purified NK cells demonstrated an increased expression of IL-10 and decreased expression of IL-12Rbeta2, perforin, and granzyme B ex vivo in PV patients versus healthy controls. The NK cells from PV patients also showed impaired signal transducer and activator of transduction4 phosphorylation upon in vitro IL-12 stimulation. Moreover, NK cells from PV patients exhibited reduced IL-10 production in response to in vitro stimulation with IL-2/IL-12. Finally, IL-5 expression in NK cells was exclusively detected ex vivo in PV patients with active disease, and was lost in subsequent analyses performed during disease remission. Together these findings suggest that NK cells contribute to a T helper type 2-biased immune response in PV patients through impaired IL-12 signaling and an upregulation of IL-10 and IL-5.     

鼻部NK/T细胞淋巴瘤累及皮肤

为了探讨鼻部NK／T细胞淋巴瘤累及皮肤的临床表现、病理、免疫表型及EB病毒相关性。通过临床表现及病程，分析原发及累及部位。通过UCHL－1，CD56,多克隆CD3，CD8，CD20，TIA－1，粒酶B（GrB）等对肿瘤细胞免疫表型进行研究，EBV－EBER探针原位杂交检测肿瘤细胞阳性率分析其病因及发病。结果本例皮肤及鼻部取材组织病理表现为坏死及中等大小的异型性肿瘤细胞增生浸润，UCHL－1＋，CD56＋，CD3＋，CD8－，CD20－，TIA－1＋，granzyme B ,为NK／T细胞淋巴瘤表型。EBV瘤细胞阳性率达60％，进一步证实为鼻部NK／T细胞淋巴瘤，EBV相关性。支持鼻部NK／T细胞淋巴瘤是具有特殊免疫表型，与EB病毒有高度相关性的独立疾病，临床进展迅速，病程短，提示为高度侵袭性。     

Lichen planus and lichenoid drug-induced eruption: a histological and immunohistochemical study

Introduction Lichenoid drug eruption (LDE) shares similar features with lichen planus (LP), that could reflect the same pathogenesis. In LP, an autoimmune attack is accepted and cytotoxic T‐lymphocytes (CD8+) predominate, especially in late lesions. Apoptosis of keratinocytes may be mediated by CD8+ T and NK cells in two distinct ways: by the release of cytotoxic molecules such as perforin and granzyme B or by the Fas/FasL system. The immunological mechanisms involved in LDE are not yet fully established. Objectives Investigate immunohistological features in LP and LDE to add clues to better understand their pathogenesis. Material and methods Twenty‐two patients fulfilled all clinical, laboratory, histopathological, and follow‐up features of lichen planus (n = 16) and lichenoid drug eruption (n = 6). Classic histological features favoring LP or LDE were evaluated by two observers. HAM56, MAC387, UCHL‐1, OPD4, CD8, Granzyme B, Perforin, and ICAM‐1 antibodies were used to decorate the immune infiltrate. Results were analyzed through Pearson correlation, Student’s t‐test, and linear discriminant analysis. Results A higher number of necrotic keratinocytes as well as plasma cells and eosinophils within inflammatory cells were associated with LDE diagnosis. Only in LDE, a correlation was found between the number of T and CD8+ cells and between the number of granzyme B+ cells and apoptotic keratinocytes. Conclusion Our findings suggest a more important role of CD8+ granzyme B‐containing cells in LDE group, being its synthesis associated with more intense apoptosis. So, LP and LDE may have a somewhat distinct pathogenesis.     

Scarring skin lesions of discoid lupus erythematosus are characterized by high numbers of skin-homing cytotoxic lymphocytes associated with strong expression of the type I interferon-induced protein MxA

BACKGROUND: Infiltrating T lymphocytes are considered to play a major pathological role in skin lesions of cutaneous lupus erythematosus (CLE), a cutaneous autoimmune disease of unknown aetiology. Earlier histological studies revealed that the inflammatory infiltrate in CLE skin lesions is predominantly composed of T lymphocytes, with a slight predominance of CD4+ over CD8+ T cells, but failed to explain the development of scarring skin lesions, characteristic for chronic discoid lupus erythematosus (CDLE). Because recent investigations have highlighted the relevance of cytotoxic lymphocytes in autoimmune tissue destruction, we hypothesized that the scarring CDLE lesions might be caused by cytotoxic T lymphocytes. OBJECTIVES: To analyse skin biopsies of 15 patients with CLE [10 female, five male; localized CDLE (lCDLE), n = 5; disseminated CDLE (dCDLE), n = 5, subacute CLE (SCLE), n = 5] and five control biopsies taken from healthy controls and to characterize the inflammatory infiltrate. Methods We used immunohistochemistry, including staining for the cytotoxic molecule granzyme B, the skin-homing molecule cutaneous lymphocyte antigen (CLA) and the protein MxA, which is specifically induced by type I interferons (IFNs). RESULTS: We found a strong coexpression of granzyme B and CLA on lesional lymphocytes of patients with scarring lCDLE and dCDLE, which was significantly enhanced when compared with nonscarring SCLE and healthy controls. The increased expression of granzyme B was closely associated with the lesional expression of the type I IFN-induced protein MxA. CONCLUSIONS: Our results provide evidence that type I IFNs and potentially autoreactive cytotoxic lymphocytes targeting adnexal structures are highly associated with scarring lupus erythematosus lesions and might be responsible for their scarring character.     

CD56 highCD16 - NK cell involvement in cutaneous lichen planus

Lichen planus is an inflammatory disease of the skin and mucous membranes characterized by vacuolization of basal keratinocytes associated with a prominent junctional lymphocyte infiltrate which comprises T?lymphocytes, NK cells, myeloid and plasmacytoid dendritic cells. Basal keratinocyte damage is considered as being a consequence of a lymphocytic cytotoxic attack, mostly mediated by perforin+CD8+ T?lymphocytes. NK cells have been described to infiltrate inflamed skin and significantly contribute to the amplification of immune-mediated skin diseases, thanks to their cytotoxic activity and the release of pro-inflammatory cytokines. Here, we investigated the characteristics and functional properties of NK lymphocytes involved in lichen planus. Double staining immunohistochemistry showed a considerable number (6.42 ± 2.2% of the total cellular infiltrate) of CD3-CD56+ cells in early lichen planus lesions, mostly distributed in the papillary dermis and at the epidermal-dermal interface. Skin NK cells isolated from lichen planus lesions belong to the CD56highCD16- subset, are highly positive for perforin and natural cytotoxic receptors NKG2D and NKp44, and, in accordance with their phenotype, are negative for KIRs receptors CD158a and CD158b. Skin CD56highCD16- NK cells display a CCR6+CXCR3+CCR5+ChemR23+ chemokine receptor asset for homing into inflamed skin. In terms of cytokine release, skin CD56highCD16- NK cells are able to secrete IFN-γ, TNF-α and hardly release IL-22, IL-17 and IL-4. Overall, our data propose a pro-inflammatory role of NK lymphocytes in lichen planus.     

Immunohistochemical features of cutaneous granulomas in primary immunodeficiency disorders: a comparison with cutaneous sarcoidosis

Background:  Cutaneous granulomas can occur in patients with a primary immunodeficiency disorder. In some cases, an infectious cause cannot be revealed. The pathogenesis of these granulomas still remains to be elucidated. The aim of this study was to study differences or overlap between these rare granulomas and sarcoidosis-related granulomas.
Methods:  Markers for T-cell subsets (CD3, CD4, CD8 and CD45RO), Langerhans' cells (CD1a), macrophages (CD68), B cells (CD20) and NK cells (CD56) were stained immunohistochemically. The amount of CD4+ and CD8+ cells in the granulomas was counted. Results were compared with the CD4+/CD8+ ratio in peripheral blood.
Results:  In the granulomas of two of three patients with a primary immunodeficiency disorder, the cytotoxic T cells (CD8+) outnumbered the T-helper cells (CD4+) with a counted CD4+/CD8+ ratio <<1. In contrast, the granulomas in the cutaneous sarcoidosis patients showed a predominance of CD4+ cells, with CD4+/CD8+ ratios >2.
Conclusions:  A lower CD4+/CD8+ ratio was found in the cutaneous granulomas of patients with a primary immunodeficiency disorder (unclassified combined immunodeficiency, autoimmune lymphoproliferative syndrome and ataxia teleangiectasia) as compared with the patients with cutaneous sarcoidosis. The possible implications of these findings are discussed in this paper.     

Evidence of in situ cytotoxicity in American cutaneous leishmaniasis

The role of cytotoxicity in the defense mechanisms or pathogenesis of human cutaneous leishmaniasis is not yet well known. In the present work we assessed the presence of NK, CD8+ and CD45RO+ T cells, as well as the expression of a molecule associated with cytotoxic properties (TIA-1) in the lesions of cutaneous leishmaniasis. CD8+ T cells, NK and activated T cells were found within the dermal cell infiltrate. We found a heterogeneous but usually strong expression of TIA-1, a marker of cytotoxic granules of T and NK cells, in human cutaneous leishmaniasis lesions. These data suggest that cytotoxic activity occurs in situ in American cutaneous leishmaniasis and that both NK cells and activated CD8+ T cells are involved in this reaction.     

The expression of cytotoxic mediators is altered in mononuclear cells of patients with melanoma and increased by interferon-alpha treatment

BACKGROUND: The role of cytotoxic cells in the control of cancer is now well established. OBJECTIVES: To evaluate the expression of perforin and granzyme A in cytotoxic cells of patients with melanoma and to look for a link between this expression and natural tumour progression; to check if interferon (IFN)-alpha administration increased expression of cytotoxic mediators; and to evaluate if this increase was correlated with the antitumoral effect of IFN-alpha. METHODS: To determine in patients with melanoma the expression of the cytotoxic mediators perforin and granzyme A in peripheral blood natural killer (NK) and T cells, we used flow cytometry before and after IFN-alpha administration. RESULTS: Compared with healthy volunteers, we observed in 82 patients a low percentage of NK cells harbouring perforin [75% (95% confidence interval (CI) 70-79) vs. 92% (95% CI 89-95), P < 0.001] and granzyme A [48% (95% CI 41-55) vs. 73% (95% CI 66-81), P < 0.001]. By contrast, a high percentage of T cells, and particularly of CD56+ T cells, expressed perforin [56% (95% CI 41-71) vs. 28% (95% CI 18-38), P < 0.001], whereas a low percentage of CD56+ T cells expressed granzyme A [30% (95% CI 24-36) vs. 54% (95% CI 43-65), P < 0.001]. In untreated patients, the percentage of CD56+ T cells expressing granzyme A was higher in progressors than in nonprogressors [49% (95% CI 39-58) vs. 16% (95% CI 0-33), P = 0.003]. We followed cytotoxic mediator expression in 17 patients treated with IFN-alpha. IFN-alpha administration increased granzyme A expression in NK cells [44% (95% CI 27-61) and 65% (95% CI 54-76) before and after treatment, respectively, P = 0.010], rather than perforin expression, whereas expression of both perforin [46% (95% CI 30-62), and 58% (95% CI 44-73), P = 0.112] and especially granzyme A [27% (95% CI 14-40) vs. 45% (95% CI 26-64), P = 0.016] was increased in CD56+ T cells after IFN-alpha administration. Yet, this effect was not correlated with the clinical response to IFN-alpha. CONCLUSIONS: Thus, the expression of cytotoxic mediators is altered in cytotoxic cells of patients with melanoma, and increased under IFN-alpha administration.     

Cutaneous intravascular anaplastic large cell lymphoma

Intravascular lymphoma (IL) is a rare variant of non‐Hodgkin lymphoma with a predilection for skin. Most reported cases are large B cell lymphomas. Intravascular anaplastic large cell lymphoma (IALCL) is extremely rare. Retrospective analysis of a case of cutaneous IALCL was performed. Hematoxylin and eosin stained sections and immunohistochemical staining results were analyzed. The patient was a 47‐year‐old woman who had developed multiple erythematous patches and plaques on her back. The lesions responded well to CHOP (cyclophosphamide, hydroxydoxorubicin, oncovin, prednisone) chemotherapy, but relapsed shortly after therapy. The patient was surviving with the disease for eight years but was ultimately lost to follow up. Histopathologically, the neoplasm evolved from IL to extravascular lymphoma. This was showed in biopsies obtained at different stages of the disease. The lymphoma cells stained positively for CD30, CD45, CD3, CD4, CD5 and Ki67, and lacked expression of anaplastic lymphoma kinase (ALK), CD8, CD45RA, CD45RO, CD20, CD79, CD56, perforin and granzyme B. Our results suggest that IALCL represents a distinct subtype of IL and is histopathologically and biologically different from IL with B, NK or T cell phenotype. Wang L, Li C, Gao T. Cutaneous intravascular anaplastic large cell lymphoma.     

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。     

Granzyme-B-containing lymphocyte involvement in epidermal injury in graft-versus-host disease

BACKGROUND: Skin lesions from graft-versus-host disease (GVHD) show histological features of epidermal cell death with lymphocyte infiltration. Perforin and granzyme B are involved in the process of apoptosis induced by cytotoxic T lymphocytes (CTL). OBJECTIVE: To elucidate the role of CTL in the mechanism of epidermal injury in GVHD. METHODS: We studied immunohistochemical staining for granzyme B and perforin in the skin lesions of 8 patients who developed GVHD after bone marrow transplantation. RESULTS: Granzyme-B-positive lymphocytes were CD8 positive and were observed in the epidermis of 3 out of 6 specimens in acute GVHD, and of 5 specimens of chronic GVHD except for 1 sclerotic type in which it was negative. Perforin-positive lymphocytes were observed in the epidermis of the specimens from 1 acute and 1 chronic GVHD. CONCLUSIONS: Granzyme B derived from CTL may be involved in the mechanisms of epidermal injury in GVHD.     

CD30+ clonal T‐cell lymphoid proliferation of the skin in a patient with hypereosinophilic syndrome

We report a hitherto undescribed unusual CD30+ clonal T‐cell proliferation in a 46‐year‐old man with the lymphocytic variant of hypereosinophilic syndrome with a 17‐year history of pruritus, generalized persistent papulonodular skin lesions and peripheral blood hypereosinophilia. A skin biopsy showed an eosinophil‐rich infiltrate with small to medium‐sized CD30+ lymphocytes and Churg‐Strauss granulomas. Peripheral blood flow cytometry revealed an aberrant T‐cell clone which, molecular genetically, was identical to the T‐cell clone detected in the skin. No genetic aberrations of platelet‐derived growth factor receptor alpha (PDGFRA), FIP1L1‐PDGFRA, PDGFRB or FGFR1 were found. The skin lesions showed transient response to systemic and topical corticosteroids. The skin lesions represent cutaneous involvement by clonal T‐cells in hypereosinophilic syndrome and differ from known cutaneous CD30+ lymphoproliferative disorders.