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.     

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.     

Impaired T‐cell‐dependent protection against Leishmania major infection in HIV‐positive patients is associated with worsened disease outcome

Cutaneous leishmaniasis (CL) patients coinfected with HIV are known to show a more severe, prolonged course of disease; the immunological basis is not known. We now assessed clinical features, sera and skin biopsies of HIV⁺ and HIV^? patients with CL to identify drivers of increased susceptibility to Leishmania. CL lesion numbers, surface, and healing duration were significantly increased in HIV⁺ as compared to HIV^? patients (2.5, 14 and >4‐fold, respectively). Patients with HIV infection exhibited lower serum Leishmania‐specific IgG levels and decreased IL‐6 and IL‐8. Most importantly, dramatically decreased numbers of CD4⁺ T cells (approximately eightfold), but not CD8⁺ cells, together with fewer CXCR3⁺ Th1 cells, fewer Foxp3⁺ effector/regulatory T cells, and reduced levels of IFN‐γ expression were found in lesional skin. Our findings suggest that compromised CD4⁺ T‐cell responses may be responsible for worsened disease outcome leading to defects in parasite elimination in the absence of sufficient numbers of IFN‐γ‐producing Th1 cells.     

Expression analysis of PD‐1 and Tim‐3 immune checkpoint receptors in patients with vitiligo; positive association with disease activity

The contribution of immune checkpoint receptors in the immunopathogenesis of various autoimmune diseases has been addressed in previous reports. In this study,  the expression profile of T‐cell immunoglobulin and mucin‐domain containing‐3 (Tim‐3) and programmed cell death‐1 (PD‐1) checkpoint molecules was investigated in CD8⁺ T cells of Vitiligo patients. The association of Tim‐3 and PD‐1 expression with disease activity was also explored. The frequency of Tim‐3⁺/PD‐1⁺/CD8⁺ T cells in 30 patients with vitiligo and 30 sex‐ and age‐matched controls was determined by flow cytometry. CD8⁺ T cells were then positively isolated by magnetic beads, and the mRNA expression of PD‐1 and Tim‐3 was determined by TaqMan‐based real‐time PCR. To measure the cytokines production, PBMCs were stimulated with PMA/ionomycin and concentrations of IL‐4, IFN‐γ and TNF‐α were measured in culture supernatants by ELISA. Disease activity of patients with vitiligo was determined using the Vitiligo Area Severity Index. Patients with vitiligo have significantly shown more expression of Tim‐3 and PD‐1 on their CD8⁺ T cells compared with controls. Expression analysis of Tim‐3 mRNA, but not PD‐1, confirmed the results obtained from flow cytometry. While the production levels of TNF‐α and IFN‐γ were found higher by patients with vitiligo, IL‐4 production was lower in patients compared with controls. A direct association was observed between the Tim‐3 and PD‐1 expression and also the production of pro‐inflammatory cytokines with disease activity of patients with vitiligo. Our results indicate that Tim‐3 and PD‐1 are involved in immune dysregulation mechanisms of CD8⁺ T cells in vitiligo and may introduce as potential biomarkers for disease progression and targeted immunotherapy.     

Effective induction of melanoma‐antigen‐specific CD8+ T cells via Vγ9γδT cell expansion by CD56high+ Interferon‐α‐induced dendritic cells

Dendritic cells (DCs) can be differentiated from CD14⁺ monocytes in the presence of interferon‐α (IFNα) and granulocyte/macrophage‐colony stimulating factor (GM‐CSF) in vitro and are known as IFN‐DCs. Circulating blood CD56⁺ cells expressing high levels of CD14, HLA‐DR and CD86 have been shown to spontaneously differentiate into DC‐like cells in vitro after their isolation from blood. We show here that IFN‐DCs expressing high levels of CD56 (hereafter, CD56^high+ IFN‐DCs) can be differentiated in vitro from monocytes obtained as adherent cells from healthy donors and patients with metastatic melanoma. These cells expressed high levels of CD14, HLA‐DR and CD86 and possessed many pseudopodia. These CD56^high+ IFN‐DCs may be an in vitro counterpart of the circulating CD56⁺ CD14⁺ CD86⁺ HLA‐DR⁺ cells in blood. Conventional mature DCs differentiated from monocytes as adherent cells in the presence of GM‐CSF, IL‐4 and TNF‐α (hereafter, mIL‐4DCs) did not express CD56 or CD14. In contrast to mIL‐4DCs, the CD56^high+ IFN‐DCs exhibited a stronger capacity to stimulate autologous CD56⁺ Vγ9γδT cells highly producing IFNγ in the presence of zoledronate and IL‐2. The CD56^high+ IFN‐DCs possessing HLA‐A*0201 effectively induced Mart‐1‐modified melanoma peptide (A27L)‐specific CD8⁺ T cells through preferential expansion of CD56⁺ Vγ9γδT cells in the presence of A27L, zoledronate and IL‐2. Vaccination with CD56^high+ IFN‐DCs copulsed with tumor antigens and zoledronate may orchestrate the induction of various CD56⁺ immune cells possessing high effector functions, resulting in strong immunological responses against tumor cells. This study may be relevant to the design of future clinical trials of CD56^high+ IFN‐DCs‐based immunotherapies for patients with melanoma.     

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.     

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.     

Decreased interleukin‐21 expression in skin and blood in advanced mycosis fungoides

Interleukin (IL)‐21 is regarded as a potent antitumor agent, which increases the cytotoxicity of both natural killer (NK) and CD8⁺ T cells. In this study, we investigated the role of IL‐21 in mycosis fungoides (MF). IL‐21 mRNA expression levels in patch and plaque MF were significantly higher than those in normal skin. IL‐21 mRNA expression levels in tumor MF were significantly decreased compared with those in patch and plaque MF. Interestingly, mRNA expression levels of IL‐21 in MF lesional skin significantly correlated with those of T‐helper type‐1 cytokines/chemokines such as CXCL10, CXCL11 and γ‐interferon. Immunohistochemistry showed that IL‐21 was expressed by keratinocytes in patch and plaque MF. Furthermore, serum IL‐21 levels in patients with tumor MF were significantly lower than those of healthy controls and plaque MF. Thus, IL‐21 expression was significantly downregulated in skin and blood of patients with tumor MF, which may contribute to progression of MF. Our study suggests that recombinant IL‐21 would be a promising therapy for MF.     

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.     

Increase of interleukin‐10‐producing B cells associated with long‐term remission after i.v. immunoglobulin treatment for pemphigus

We present a refractory case of pemphigus vulgaris that achieved long‐term remission after i.v. immunoglobulin treatment (IVIG). We evaluated the fluctuation of circulating interleukin‐10‐producing B cells (B10 cells) during the course in our case and other three patients with pemphigus treated with IVIG without clinical remission. B10 cells were observed predominantly in CD1d^–, CD5^–, CD9^– and CD27⁺ populations among CD19⁺ cells in healthy controls, as well as in patients with pemphigus. The frequency of B10 cells among CD19⁺ cells increased in our case, but not in the other three patients without clinical remission, which leads to speculation on the association between the increase of B10 cells and the achievement of long‐term remission after IVIG treatment.     

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.     

Decrease in circulating Th17 cells correlates with increased levels of CCL17, IgE and eosinophils in atopic dermatitis

Background

Clinical significance of circulating CD4⁺ T cell subsets, including T-helper (Th)1, Th2, Th17 and regulatory T (Treg) cells, in patients with atopic dermatitis (AD) remains unclear. No previous studies have simultaneously evaluated the four T cell subset profiles in AD.

Objective

The aim of the present study was to explore whether the percentage of these four subsets of CD4⁺ T cells correlate to the severity parameters of AD patients.

Methods

Intracellular expression of interferon (IFN)-γ, interleukin (IL)-4, IL-17 and forkhead box P3 (Foxp3) in CD4⁺ T cells was evaluated in peripheral blood mononuclear cells from normal controls and patient with AD as well as with chronic eczema using a flow cytometer. Serum CCL17 levels were measured as an objective severity parameter of AD together with percentage of eosinophils and serum IgE levels.

Results

In AD patients, the number of Th1 (IFN-γ⁺) and Th17 (IL-17⁺) subsets was significantly decreased, but that of Th2 (IL-4⁺) and Treg (Foxp3⁺) subsets was similar to that of normal controls. The T cell subset profiles of patients with chronic eczema were not different with those of normal controls. The frequency of Th17cells, particularly that of the IFN-γ^negaIL-17⁺ subset, showed a significant negative correlation with CCL17, IgE and eosinophil levels in AD patients. This was, however, not the case in Th1, Th2 and Treg cells.

Conclusion

Decreased circulating Th17 cells might contribute to activity of AD.     

Naïve CD4+ T cells from patients with atopic dermatitis show an aberrant maturation towards IL-4-producing skin-homing CLA+ cells

Abstract: Overproduction of interleukin‐4 (IL‐4) has been reported in lesional and in peripheral T cells from patients with atopic dermatitis (AD). It is not clear whether the development of IL‐4‐producing T helper type 2 (Th2) cells from naïve precursors is an intrinsic phenomenon of T cells or whether other, extrinsic factors play a significant role. To analyze these alternatives, we investigated the IL‐4 production of effector T cells generated in vitro from highly purified CD4+ CD45RA+ naïve T cells in the absence of signals derived from antigen‐presenting cells. Effector T cells generated from naïve precursors from both AD and healthy donors produced comparable amounts of IL‐4 after restimulation. Priming in the presence of exogenous IL‐4 enhanced the production of IL‐4 while neutralizing endogenously produced IL‐4 abolished IL‐4 production similarly in atopic and healthy T cells. A subset of effector T cells acquired the expression of the cutaneous lymphocyte antigen (CLA). The frequency of CLA+ T cells was not different between atopic and healthy donors. CLA+ T cells, differentiated from naïve atopic, but not healthy T cells, showed a preferential Th2 cytokine profile as assessed by intracellular cytokine staining. Also effector T cells derived from atopic patients without dermatitis tended to show this imbalance, although it was not significantly different to healthy controls. This Th2 cytokine profile did not develop when naïve T cells were cultured in the presence of IL‐12. In conclusion, high IL‐4 production in developing T cells from AD patients was associated with CLA expression, the net IL‐4 production of all effector CD4+ T cells, however, was similar to IL‐4 production by T cells from healthy donors.     

Papuloerythroderma‐like cutaneous involvement of a CD62L− subclone of T‐cell prolymphocytic leukemia

We report the case of an 88‐year‐old Japanese man with erythrodermic involvement of T‐cell prolymphocytic leukemia (T‐PLL). He had a history of pharyngeal diffuse large B‐cell lymphoma successfully treated with polychemotherapy including cyclophosphamide and epirubicin, 6 years before the current illness. He presented with numerous reddish, coalescing, flat‐topped papules on the trunk and extremities, sparing the skin folds of the abdomen, the features of which mimicked those of papuloerythroderma. Immunohistochemistry showed perivascular and epidermotropic infiltration of CD3⁺ CD4⁺ T cells in the cutaneous lesion. However, flow cytometric analysis revealed that the skin infiltrating T cells were negative for surface CD4, and that CD3⁺ CD4^? CD8^? cells made up 92% of the T‐cell fraction of peripheral blood. The circulating atypical T cells had a round or oval nucleus and prominent nucleoli, and the deletion of chromosomes 6q, 13 and 17. These cytological profiles were consistent with those of T‐PLL and distinct from those of Sézary cells. The same T‐cell clone was detected in the cutaneous lesion and peripheral blood, but the expression of CD62L was absent in the skin infiltrates and present in the circulating cells. No specific mutation was detected in STAT3 or STAT5B. Although low‐dose oral etoposide had a beneficial effect on the skin rash, a fatal crisis of marked leukocytosis (169 × 10³/μL) occurred 19 months after the illness onset. CD62L‐leukemic cells of T‐PLL may infiltrate the skin to form papuloerythroderma‐like cutaneous lesions.     

Immunoglobulin G4‐related disease presenting with prurigo: Circulating T‐helper 2 cells may be involved in the pathogenesis

We report a case of immunoglobulin G4‐related disease (IgG4‐RD) which presented with prurigo on the trunk and extremities. A 66‐year‐old man had a 2‐month history of itchy erythematous papules on his trunk and extremities. Bilateral eyelid swelling and enlargement of the submandibular and parotid glands were also observed. Computed tomography revealed pleural thickening and diffuse pancreatic enlargement. Serum levels of IgG4 were markedly increased. A biopsy specimen obtained from an erythematous papule showed a perivascular inflammatory infiltrate of lymphocytes with eosinophils in the dermis, whereas a parotid gland biopsy revealed an infiltrate of abundant IgG4‐positive plasma cells. Treatment with prednisolone resulted in improvement of the skin and other lesions along with a decrease in IgG4 serum levels. A flow cytometric assay revealed that percentages of interleukin (IL)‐4‐ and IL‐13‐producing CD4⁺ T cells were markedly higher in the circulation of the IgG4‐RD patient than in that of healthy subjects. Moreover, those populations dramatically decreased after treatment. Thus, prurigo may be a skin manifestation of IgG4‐RD and T‐helper 2 cells may contribute to the pathogenesis.     

Propionibacterium acnes vaccination induces regulatory T cells and Th1 immune responses and improves mouse atopic dermatitis

Abstract: Atopic dermatitis (AD) is a chronic disease characterized by a polarized Th2 immune response. Propionibacterium acnes (P. acnes) has been shown to elicit strong Th1 immune responses. We hypothesized that the host immune response to P. acnes will prevent the development of AD. To demonstrate this hypothesis, we investigated the effect of P. acnes vaccination on AD that occurs in keratin 14/driven caspase‐1 transgenic mouse. Vaccination with low dose of P. acnes successfully prevented clinical manifestations in the skin of AD mice associated with systemic and cutaneous increased expression of Th1‐type cytokines but without suppression of Th2 cytokines. Interestingly, the numbers of IFN‐γ⁺T cells, FoxP3⁺CD4⁺CD25⁺T cells (nTreg) and IL‐10⁺T cells (Tr1) were significantly increased in the spleen. P. acnes vaccination has effects to alter the cytokine milieu and may be useful for the improvement of atopic symptom.     

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.     

Role of the subgroups of T,B, natural killer lymphocyte and serum levels of interleukin‐15, interleukin‐21 and immunoglobulin E in the pathogenesis of urticaria

The immunological characterization in the pathogenesis of urticaria, mainly regarding cytokine profile, needs more investigation. In this study, subgroups of the T, B and natural killer (NK) lymphocyte from peripheral blood and serum levels of interleukin (IL)‐15, IL‐21 and immunoglobulin (Ig)E were examined in patients with acute urticaria (AU) and chronic urticaria (CU). Moreover, symptom scores and course of the patients were assessed. The percentage of NK cells and the ratio of CD4⁺/CD8⁺ increased, however, CD8⁺ decreased in CU compared to controls (P < 0.01). But no significant changes of T, B and NK lymphocyte were found in AU. IL‐15 and IL‐21 significantly decreased in AU and CU, but IgE increased. CU with a positive autologous serum skin test were more likely to be associated with longer course and higher CD3⁺, B cells and IL‐21, and lower IgE (P < 0.01). Weak negative correlations were demonstrated between CD3⁺, CD8⁺ and scores in CU (r = ?0.23, ?0.25, P < 0.05). Significant correlations were found between B cells and scores and course in CU (r = 0.49, 0.65, P < 0.01). Moreover, a significant correlation was found between IL‐21 and IgE (r = 0.42, P < 0.01) in CU. But no significant correlations were found in AU. Our findings supported the concept that both humoral immunity and cellular immunity dysregulation in the pathogenesis of urticaria – mainly related to the decrease of the serum levels of IL‐15 and IL‐21 – may induce the increasing expression of IgE produced by B cells.