A novel surface molecule of Th2- and Tc2-type cells, CRTH2 expression on human peripheral and decidual CD4+ and CD8+ T cells during the early stage of pregnancy

It has been demonstrated that pregnancy induces the immunomodulation of cytokine responses away from the Th1 paradigm and towards the Th2 paradigm. In this study, we examined the expression of CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2) on decidual CD4+ and CD8+ T cells during the early stages of pregnancy. Examination of the cytokine profile revealed that CRTH2 was expressed on CD4+-type-2 T helper (Th2-type) and CD8+-type 2 T cytotoxic (Tc2-type) cells. The percentages of CRTH2+ cells in CD3+/CD4+ T cells and CD3+/CD8+ T cells were significantly higher in the decidua than in the peripheral blood. These results indicate the significance of Th2- and Tc2-type cells of the decidua in the maternal immune system, presumably through their production of cytokines which may contribute to the maintenance of pregnancy.     

Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine

Helper T cells are classified into Th1 and Th2 subsets based on their profiles of cytokine production. Th1 cells are involved in cell-mediated immunity, whereas Th2 cells induce humoral responses. Selective recruitment of these two subsets depends on specific adhesion molecules and specific chemoattractants. Here, we demonstrate that the T cell-directed CC chemokine thymus and activation-regulated chemokine (TARC) was abundantly produced by monocytes treated with granulocyte macrophage colony stimulating factor (GM-CSF) or IL-3, especially in the presence of IL-4 and by dendritic cells derived from monocytes cultured with GM-CSF + IL-4. The receptor for TARC and another macrophage/dendritic cell-derived CC chemokine macrophage-derived chemokine (MDC) is CCR4, a G protein-coupled receptor. CCR4 was found to be expressed on approximately 20% of adult peripheral blood effector/memory CD4+ T cells. T cells attracted by TARC and MDC generated cell lines predominantly producing Th2-type cytokines, IL-4 and IL-5. Fractionated CCR4+ cells but not CCR4- cells also selectively gave rise to Th2-type cell lines. When naive CD4+ T cells from adult peripheral blood were polarized in vitro, Th2-type cells selectively expressed CCR4 and vigorously migrated toward TARC and MDC. Taken together, CCR4 is selectively expressed on Th2-type T cells and antigen-presenting cells may recruit Th2 cells expressing CCR4 by producing TARC and MDC in Th2-dominant conditions.     

Characterization of NKT Cells in Human Peripheral Blood and Decidual Lymphocytes

PROBLEM: To examine whether natural killer (NKT) cells are present in human pregnancy decidua. METHOD OF STUDY: We calculated the percentage of CD3+CD161+Valpha 24+-NKT cells in peripheral blood and early pregnancy decidua, and analyzed intracellular cytokines, interleukin (IL)-4 and interferon (IFN)gamma in NKT cells using flow cytometry. RESULTS: A distinct subset of CD3+ CD161+ lymphocytes expressing an invariant antigen receptor encoded by the Valpha24 and Vbeta11 segment was accumulated in the decidua. In pregnant subjects the percentages of NKT cells were significantly increased in the decidua compared with peripheral blood. Both NKT cells in the decidua and the peripheral blood had an ability to rapidly produce cytokine associated with Th1 (IFNgamma) and Th2 (IL-4). Interestingly, the percentages of IL-4 and IFNgamma producing NKT cells were significantly higher in the decidua compared with the peripheral blood. CONCLUSIONS: These findings suggest that NKT cells might control the Th1/Th2 balance by producing IL-4 and IFNgamma at the feto-maternal interface.     

Clonal Th2 cells associated with chronic hypereosinophilia: TARC-induced CCR4 down-regulation in vivo

We analyzed the expression of chemokine receptors on clonal Th2-type CD4(+)CD3(- )lymphocytes isolated from blood of two patients with chronic hypereosinophilia. First, we observed that these Th2 cells express membrane CCR5 and CXCR4 but neither CCR3 nor CCR4 when analyzed immediately after purification. However, CCR4 appeared following culture in human serum-free medium, suggesting that it was down-regulated in vivo. Indeed, patient's serum, but not control human serum, strongly down-regulated CCR4 expression on cultured Th2 cells. As high levels of TARC, a CCR4 ligand, were detected in the serum of four hypereosinophilic patients with CD3(-)CD4(+) clonal Th2 cells, we evaluated the effect of TARC neutralization in this system. Addition of a neutralizing anti-TARC mAb inhibited CCR4 down-regulation by patient's serum, indicating that circulating TARC contributed to CCR4 down-regulation on Th2 cells in vivo. Clonal Th2 cells did not secrete high levels of TARC themselves but induced a sustained production of TARC by monocyte-derived dendritic cells, a phenomenon that was inhibited by addition of blocking mAb against IL-4 receptor. We conclude that high circulating levels of TARC in serum of patients with chronic hypereosinophilia, most likely derived from antigen-presenting cells stimulated by Th2-type cytokines, induce down-regulation of CCR4 on Th2 cells in vivo.     

Prostaglandin D2 and reproduction

This review highlights recent studies investigating the role of prostaglandin (PG)D2 in reproduction. PGD2 induces sleep, allergic responses, inhibition of platelet aggregation, and relaxation of vascular and non-vascular smooth muscle, and has some roles in reproduction. Two types of PGD2 synthase are known. Lipocalin-type PGD synthase is present in cerebrospinal fluid, seminal plasma and may play an important role in male reproduction. Another PGD synthase, hematopoietic PGD synthase is present in the spleen, fallopian tube, endometrial gland cells, extravillous trophoblasts and villous trophoblasts, and perhaps plays an important role in female reproduction. Recent studies demonstrate that PGD2 is probably involved in multiple aspects of inflammation through its dual receptor systems, DP and CRTH2. CRTH2 but not DP is a chemo-attractant receptor for PGD2. Interestingly, CRTH2 is a most reliable marker for the detection of human T helper type 2 (Th2) and T cytotoxic type 2 (Tc2) cells, and the percentages of CRTH expressing CD4+-T cells and CD8+-T cells were significantly higher in the decidua especially at the implantation site, suggesting that Th2 and Tc2 cells recruit into the materno-fetal interface, in a PGD2-mediated manner. PGD2 has a very unique effect to inhibit antigen presentation by inhibition of dendritic cell (DC) migration through DP but not CRTH2. PGD2 might appear to contribute to the maintenance of pregnancy by controlling the Th1/Th2 balance and antigen presentation by DCs through its dual receptor systems, CRTH2 and DP.     

Selective recruitment of CXCR3+ and CCR5+ CCR4+ T cells into synovial tissue in patients with rheumatoid arthritis

The inflamed synovial tissue (ST) of rheumatoid arthritis (RA) is characterized by the selective accumulation of interferon gamma-producing Th1-type CD4+ T cells. In this study, we investigated whether the predominance of Th1-type CD4+ cells in the ST lesion is mediated by their selective recruitment through Th1 cell-associated chemokine receptors CXCR3 and CCR5. The lymphocyte aggregates in the ST of RA contained a large number of CD4+ T cells, which mostly expressed both CXCR3 and CCR5, but not CCR4. In contrast, the frequencies of CD4+ and CD8+ T cells expressing CXCR3 and CCR5 in the blood were significantly decreased in RA patients, compared with healthy controls (HC), although there was no difference in the frequencies of CCR4-expressing CD4+ and CD8+ T cells between RA and HC. CXCR3, CCR5, and CCR4 expression in blood CD4 + T cells and CXCR3 expression in CD8+ T cells were increased after interleukin-15 (IL-15) stimulation. Therefore, the distribution of Th1-type CD4+ T cells into the ST from the blood in RA may be associated with the local expression of chemokines, both CXCR3 and CCR5 ligands, and IL-15 may play a role in enhancing these chemokine receptors on CD4+ T cell infiltrates.     

Distribution of Th1, Th2, and Th0 and the Th1/Th2 cell ratios in human peripheral and endometrial T cells

PROBLEM: To examine whether normal pregnancy involves type 2 T-helper (Th2) immune condition or not. METHOD OF STUDY: We measured the percentage of Th0, Th1, and Th2 and the Th1/Th2 cell ratios of human peripheral blood and endometrial T cells using flow cytometry, which can analyze both the surface marker CD3, and intracellular cytokines, interleukin 4 (IL-4) and interferon gamma (IFNgamma). RESULTS: No significant differences were found in the percentages of Th1, Th2, and Th0 and the Th1/Th2 cell ratios in the peripheral blood T cells of nonpregnant women and women in early pregnancy. On the other hand, the percentage of Th1 cells was highest during the proliferative phase of the endometrium, followed by the secretory phase and early pregnancy decidua. The percentage of Th2 cells was highest in early pregnancy decidua and lowest during the proliferative phase of the endometrium. The Th1/Th2 ratio was 147.48+/-96.68 during the proliferative phase of the endometrium, 37.74+/-21.33 during the secretory phase, and 1.31+/-0.48 in the early pregnancy decidua. CONCLUSIONS: These data indicate that Th1 cells predominate in the nonpregnant endometrium, especially during the proliferative phase, while Th2 cells predominate in early pregnancy decidua.     

Accumulation of CCR4-expressing CD4+ T cells and high concentration of its ligands (TARC and MDC) in bronchoalveolar lavage fluid of patients with eosinophilic pneumonia

BACKGROUND: Th2 cells are thought to be involved in eosinophilic inflammation of the lung. CC chemokine receptor 4 (CCR4) has been identified as a specific receptor for both thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC), and is preferentially expressed on Th2 cells. OBJECTIVE: Our aim was to evaluate the role of Th2 cells in the lung of patients with eosinophilic pneumonia (EP). METHODS: The concentrations of TARC, MDC, and interleukin (IL)-5 were measured in bronchoalveolar lavage fluid (BALF) by ELISA. Proportion of CCR4-expressing CD4+ T cells (CCR4+ CD4+ T cells) was determined by flow cytometry. RESULTS: TARC and MDC concentrations in BALF were higher in patients with EP than in normal subjects. The proportion of CCR4-expressing cells among CD4+ T cells was higher in BALF than in peripheral blood of patients with EP. There was a significant correlation between the number of CCR4+ CD4+ T cells and the levels of TARC, MDC, and IL-5 in BALF of patients with EP. CONCLUSIONS: Our data suggest that Th2 cells, which express CCR4 and its ligands (TARC and MDC), contribute to the pathogenesis of EP in the lung.     

Thymus and activation-regulated chemokine in atopic dermatitis: Serum thymus and activation-regulated chemokine level is closely related with disease activity

BACKGROUND: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of TH2-type cells in lesional skin. Thymus and activation-regulated chemokine (TARC/CCL17) is a chemokine that attracts CC chemokine receptor 4-positive (CCR4+) or CCR8+ cells. OBJECTIVE: The purpose of this study was to investigate the participation of TARC in AD. METHODS: We measured serum TARC levels in 40 patients with AD, 20 healthy control subjects, and 20 patients with psoriasis. We also examined disease activity by using SCORAD score; serum soluble E-selectin, soluble IL-2 receptor, IgE, and GM-CSF levels; and eosinophil numbers in peripheral blood, as well as correlations between TARC levels and these factors. The positivity of CCR4 of CD4+CD45RO+ cells in PBMCs was examined by using FACS analysis. Immunohistochemical staining of TARC and GM-CSF was performed in the lesional skin of patients with AD. RESULTS: The serum TARC levels of patients with AD were significantly higher than those of healthy control subjects and patients with psoriasis. The serum TARC levels significantly correlated with eosinophil number (r = 0.61), SCORAD score (r = 0.60), and serum soluble E-selectin levels (r = 0.58) and weakly correlated with serum soluble IL-2 receptor levels (r = 0.34) in patients with AD. The TARC levels of patients with AD decreased after the treatment in accordance with the improvement of clinical symptoms. The CCR4 positivity of CD4+CD45RO+ cells in PBMCs of patients with AD was also higher than that of healthy control subjects. Immunohistochemical staining revealed that TARC was positive in keratinocytes in the epidermis and in vascular endothelial cells, T cells, and dendritic cells in the dermis. CONCLUSION: Serum TARC levels are associated with disease activity of AD, and TARC may play an important role in the pathogenesis of AD.     

Regulated production of the T helper 2-type T-cell chemoattractant TARC by human bronchial epithelial cells in vitro and in human lung xenografts

The chemokine TARC is a ligand for the chemokine receptor CCR4 expressed on T helper (Th)2-type CD4 T cells. Allergic airway inflammation is characterized by a local increase in cells secreting Th2-type cytokines. We hypothesized that bronchial epithelial cells may be a source of chemokines known to chemoattract Th2 cells. Regulated TARC expression was studied using normal human bronchial epithelial cells and a human lung xenograft model. TARC expression was increased in normal human bronchial epithelial cells in response to tumor necrosis factor-alpha stimulation, and further upregulation of TARC was observed with interferon (IFN)-gamma but not interleukin (IL)-4 costimulation. TARC functions as a nuclear factor (NF)-kappa B target gene, as shown by the abrogation of TARC expression in response to proinflammatory stimuli when NF-kappa B activation is inhibited. In an in vivo model, minimal constitutive TARC expression was observed in human lung xenografts. Consistent with our findings in vitro, TARC messenger RNA (mRNA) expression was upregulated in the xenografts in response to IL-1, and costimulation with IFN-gamma but not IL-4 further increased TARC mRNA and protein expression. In addition, bronchoalveolar lavage fluid from asthmatic subjects after allergen challenge contained significantly increased levels of TARC, suggesting that TARC production by bronchial epithelial cells may play a role in the pathogenesis of allergic asthma.     

A possible role of TARC in antigen-specific Th2-dominant responses in patients with Paragonimiasis westermani

BACKGROUND: Paragonimiasis westermani (Pw), a common parasitic zoonosis in Asia, is typically associated with eosinophilia. Th2 cytokines seem to have an important role in the clinical manifestations of this disease. Thymus and activation-regulated chemokine (TARC) is a potential key regulator of Th2-mediated inflammation. The purpose of the present study was to evaluate the antigen-specific Th2-dominant responses in patients with Pw. METHODS: The concentrations of cytokines and chemokines in supernatants of peripheral blood mononuclear cell (PBMC) cultures with or without antigen stimulation were measured by enzyme-linked immunosorbent assay (ELISA). TARC levels in serum from Pw patients were also evaluated by ELISA. The number of Th2 cells expressing the CC-chemokine receptor 4 (CCR4) in the peripheral blood was evaluated by flow cytometry. RESULTS: Antigen-stimulation induced production of IL-5 and IL-13, but not IFN-gamma from PBMC cultures in patients with Pw. Pw patients had elevated serum TARC levels and a higher proportion of CCR4-expressing cells among CD4+ T cells in the peripheral blood. There were also higher levels of TARC, but not IP-10, in supernatants of antigen-stimulated PBMC culture compared to unstimulated PBMC culture in patients with Pw. CONCLUSION: Our findings clarify antigen-specific Th2-dominant responses in patients with Pw and suggest a possible role for TARC in Th2-dominant responses.     

Downregulation of CXCR6 and CXCR3 in lymphocytes from birch-allergic patients

Preferential expression of chemokine receptors on Th1 or Th2 T-helper cells has mostly been studied in cell lines generated in vitro or in animal models; however, results are less well characterized in humans. We determined T-cell responses through chemokine receptor expression on lymphocytes, and cytokine secretion in plasma from birch-allergic and healthy subjects. The expression of CCR2, CCR3, CCR4, CCR5, CCR7, CXCR3, CXCR4, CXCR6, IL-12 and IL-18R receptors was studied on CD4⁺ and CD8⁺ cells from birch-allergic ( n  = 14) and healthy ( n  = 14) subjects by flow cytometry. The concentration of IL-4, IL-5, IL-10, IL-12, IFN-γ and TNF-α cytokines was measured in plasma from the same individuals using a cytometric bead array human cytokines kit. The similar expression of CCR4 in T cells from atopic and healthy individuals argues against the use of the receptor as an in vivo marker of Th2 immune responses. Reduced percentages of CD4⁺ cells expressing IL-18R, CXCR6 and CXCR3 were found in the same group of samples. TNF-α, IFN-γ, IL-10, IL-5, IL-4 and IL-12 cytokines were elevated in samples from allergic individuals. Reduced expression of Th1-associated chemokine receptors together with higher levels of Th1, Th2 and anti-inflammatory cytokines in samples from allergic patients indicate that immune responses in peripheral blood in atopic diseases are complex and cannot be simplified to the Th1/Th2 paradigm. Not only the clinical picture of atopic diseases but also the clinical state at different time points of the disease might influence the results of studies including immunological markers associated with Th1- or Th2-type immune responses.     

Pulmonary chemokines and their receptors differentiate children with asthma and chronic cough

BACKGROUND: Cough is a frequent symptom in children, but the differentiation of asthmatic cough from cough of other origins can be difficult. Chemokines recruit T lymphocytes to inflamed tissues, and the corresponding chemokine receptors are differentially expressed on T H 1 and T H 2 cells. OBJECTIVE: We sought to determine whether levels of T H 1/T H 2-related chemokines and their receptors differ in bronchoalveolar lavage fluid (BALF) from 12 children with allergic asthma, 15 nonatopic children with chronic cough, and 10 children without airway disease. METHODS: The T H 1-related (IFN-gamma-inducible protein of 10 kd [IP-10], IFN-gamma-inducible T cell alpha chemoattractant [ITAC], monokine induced by IFN-gamma [Mig], and IFN-gamma) and T H 2-related (thymus- and activation-regulated chemokine [TARC], macrophage-derived chemokine [MDC], IL-5, and IL-4) chemokines and cytokines were quantified in BALF by ELISA and a particle-based multiplex array. Percentages of pulmonary lymphocytes expressing CXCR3 + and CCR5 + (T H 1) and CCR4 + and CCR3 + (T H 2) chemokine receptors were determined in BALF by flow cytometry. RESULTS: Pulmonary CCR4 + CD4 + cells and levels of TARC and MDC were significantly increased in asthmatic children versus children with chronic cough or without airway disease. In asthmatic children CCR4 + CD4 + cells correlated positively with levels of TARC, MDC, and serum IgE levels and negatively with FEV 1 . In contrast, CXCR3 + CD8 + cells and levels of ITAC were significantly increased in children with non-atopic chronic cough compared with the other groups. In children with chronic cough, CXCR3 + CD8 + cells correlated with levels of ITAC and IFN-gamma. CONCLUSION: Pulmonary CCR4 + CD4 + and CXCR3 + CD8 + cells and their ligands TARC, MDC, and ITAC clearly differentiate asthmatic children from nonatopic children with chronic cough. The analysis of these markers could facilitate the diagnostic discrimination of asthma versus other reasons for chronic cough in children.     

CRTH2 is the most reliable marker for the detection of circulating human type 2 Th and type 2 T cytotoxic cells in health and disease

Cells expressing the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) and the chemokine C receptor (CCR)4 were consistently detected in the circulation of healthy subjects, whereas numbers of cells expressing CCR3 were much lower. While all CCR4+ cells were T cells, a small proportion of CRTH2+, and about a half of the few CCR3+ cells were basophils. Only CRTH2+ T cells contained Th2 or Tc2 cells, but neither Th0 or Tc0, nor Th1 or Tc1 cells, although not all of them produced Th2-type cytokines. By contrast, CCR4+ T cells contained both Th2 or Tc2 and Th0 or Tc0 cells and even Th1 or Tc1 cells, whereas the few CCR3+ T cells were not clearly classifiable for their cytokine profile. CRTH2+ T lymphocytes were virtually devoid of chemokine CX receptor (CXCR)3+ and CCR5+ cells, but enriched in CCR3+ and CCR4+ cells. By contrast, CCR3+ or CCR4+ T cells did not show a similar clear-cut dichotomy in the expression of CCR5/CXCR3 or CCR3/ CCR4. Subjects with atopic dermatitis or HIV infection with low levels of circulating CD4+ T cells revealed a significant increase of CRTH2+ cells within both the CD4+ and the CD8+ T cell subset. These data support the concept that at present CRTH2 is the more reliable marker for detection of both human Th2 and Tc2 cells in health and disease.     

Decrease of T-helper 2 and T-cytotoxic 2 cells at implantation sites occurs in unexplained recurrent spontaneous abortion with normal chromosomal content

BACKGROUND: In normal pregnancy, predominant type 2 cytokines help maintain pregnancy, and a T-helper (Th)1 type response is associated with unexplained recurrent spontaneous abortion (RSA). However, Th2 and T-cytotoxic (Tc)2 cells have not been localized at the implantation site in RSA. METHODS: Twenty-one cases with RSA were classified into RSA with normal chromosomal content (RSA-N, n = 10) and RSA with abnormal chromosomal content (RSA-A, n = 11). As a control, we selected 15 gestational age-matched cases of induced abortion with no history of spontaneous abortion. We immunostained paraffin-embedded decidual sections for a specific Th2 and Tc2 cell marker termed 'chemo-attractant receptor-homologous molecule expressed on Th2 cells (CRTH2)' and T-cell markers CD3 and CD8. The numbers and percentages of Th2 (CRTH2(+)CD8(-)CD3(+)) and Tc2 (CRTH2(+)CD8(+)) cells were compared between the decidua basalis and decidua parietalis. RESULTS: Th2 and Tc2 cells accumulated in the decidua basalis in normal pregnancy. Accumulation of Tc2 cells and both Th2 and Tc2 cells decreased in the decidua basalis in RSA-A and RSA-N respectively. The number and percentage of Th2, and Tc2 cells in the decidua parietalis were similar in normal pregnancy, RSA-A and RSA-N. CONCLUSION: Decreased Th2 and Tc2 cells at the implantation site may contribute to RSA-N.     

Differential expression of thymus and activation regulated chemokine and its receptor CCR4 in nodal and cutaneous anaplastic large-cell lymphomas and Hodgkin's disease.

Recent studies demonstrated that Hodgkin/Reed-Sternberg (H/RS) cells in Hodgkin's disease (HD) express thymus and activation-regulated chemokine (TARC), whereas reactive lymphocytes surrounding H/RS cells express its ligand, CC-chemokine receptor 4 (CCR4). Because in vitro studies showed that CCR4 expression is a marker for lymphocytes bearing a T-helper 2 (Th2) phenotype, it was suggested that expression of TARC is a new immune escape mechanism in HD. To find out whether this mechanism might also be operative in CD30+ malignant lymphomas other than HD, TARC and CCR4 expression was investigated by immunohistochemistry on paraffin and frozen-tissue sections of 39 nodal CD30+ anaplastic large cell lymphomas (ALCL), including 27 ALK-negative and 12 ALK-positive ALCL, 25 primary cutaneous CD30+ ALCL, including 11 patients with lymphomatoid papulosis, and 31 cases of HD. TARC was expressed by the neoplastic cells in 12/27 (44%) nodal ALK-negative ALCL and all cases of classic HD, but not in nodal ALK-positive ALCL (0/12) and only rarely in primary cutaneous CD30+ ALCL (3/25). In contrast, CCR4 was expressed by the neoplastic cells in 9/9 cutaneous CD30+ ALCL, and in 9/15 (60%) nodal ALK-negative ALCL, but only in 1/4 (25%) nodal ALK-positive ALCL and not by the H/RS cells in HD (0/8). Apart from three cases of HD showing 10 to 15% CCR4-positive lymphocytes surrounding TARC-positive H/RS cells, CCR4-positive reactive T cells were few (<5%) in all other cases studied. Our results demonstrate a differential expression of TARC and CCR4 in different types of CD30+ malignant lymphomas. The small number of CCR4-positive reactive T cells in most cases studied argues against an important role of TARC expression in the evasion of antitumor responses.     

Preferential expression of T(h)2-type chemokine and its receptor in atopic dermatitis

Lesional skin of patients with atopic dermatitis (AD) is histologically characterized by hypertrophy of the skin, and the infiltration of a large number of eosinophils and T cells into the dermis. Recent studies have indicated that Th2 cells play a crucial role in the pathogenesis of AD skin. Chemokines and their receptors are implicated in the development of symptoms of various skin diseases such as AD and psoriasis vulgaris (psoriasis). We have examined the in situ expression of a typical Th2-type chemokine, thymus- and activation-regulated chemokine (TARC), and its receptor (CCR4) using immunohistochemical techniques. TARC was found to be highly expressed in the basal epidermis of the lesional skin of AD patients and only slightly in the non-lesional skin. On the other hand, no positive cells were seen in the lesional skin of psoriasis. Consistently, CCR4+ cells were present predominantly in the lesional skin of AD patients, but not in the non-lesional skin. In contrast, in the lesional skin of psoriasis patients, cells positive for CCR5, which is expressed on Th1 cells, were abundantly present. Interestingly, psoralen plus ultraviolet A therapy reduced the number of CCR4+ cells in the AD skin lesions. These results suggest that Th2-type cytokines such as TARC are involved in the pathogenesis of skin lesions in AD patients through the preferential recruitment of Th2 cells.     

The assignment of chemokine-chemokine receptor pairs: TARC and MIP-1 beta are not ligands for human CC-chemokine receptor 8.

Identification of chemokine receptors and their associated ligands is crucial to the understanding of most immune reactions. Three human chemokines [I-309, thymus and activation-regulated chemokine (TARC) and macrophage inflammatory protein-1beta (MIP-1beta)] have been reported to be ligands for CC-chemokine receptor 8 (CCR8). In this report, we present evidence that TARC and MIP-1beta did not bind to or induce chemotaxis through CCR8 on a stable transfected cell line (1D-21) and did not bind to CCR8 on in vitro differentiated human CD4(+) Th(2) cell cultures. Also, I-309-dependent calcium mobilization in 1D-21 cells and in Th(2) cells was desensitized by I-309 but not by MIP-1beta or TARC. These results provide strong evidence that, at physiologically relevant concentrations, I-309 is the only known human ligand for CCR8. These data also provide a framework for suggesting minimum requirements for the assignment of chemokine receptor-ligand pairs.     

No difference in natural-killer-T cell population, but Th2/Tc2 predominance in peripheral blood of recurrent aborters

PROBLEM: The aim of this study was to assess the natural-killer-T (NKT) cell population and cytokine expression in the peripheral blood of women with a history of recurrent spontaneous abortion (RSA). METHOD OF STUDY: The percentages of CD3+ CD4- CD8- TCRValpha24+ Vbeta11+-NKT cells and cells expressing intracellular interferon (IFN)-gamma, interleukin (IL)-4, and tumor necrosis factor (TNF)-alpha either with CD4+ or CD8+ cells were measured by flow cytometry at the midluteal phases in 15 RSA women and 15 fertile control women. RESULTS: No significant differences in the NKT cell percentages were found between RSA and control women. However, in RSA women, the CD4+ IL-4+ cell and CD8+ IL-4+ cell percentages were significantly higher, and the Th1/Th2 and Tc1/Tc2 cell ratios were significantly lower, than those in the control. CONCLUSIONS: Th2/Tc2 dominance was found in the general circulation of RSA women; this finding provokes a new controversy on the Th1/Th2 balance concerning RSA etiology.     

Increased T-cell activation in decidua parietalis compared to decidua basalis in uncomplicated human term pregnancy

PROBLEM: The aim of this study was to quantify and compare activated T cells in term decidua basalis and parietalis using flow cytometry. METHOD OF STUDY: Term decidua basalis and parietalis samples were obtained from 20 placentas collected after elective caesarean section. Percentages of leukocyte subclasses within the CD45+ cell fraction and activated T cells were determined by flow cytometry. RESULTS: There was no significant difference in CD45+, CD14+, CD19+, and CD3+ cell percentages. However, within the CD3+ population, there were significantly more T-cell receptor-gamma(delta)+ (TCR-gamma(delta)-) and CD8+ cells in decidua parietalis compared with decidua basalis. More importantly, percentages of T cells expressing CD25, human leukocyte antigen (HLA)-DR, CD45RO, and CD69 markers were significantly increased in decidua parietalis. CONCLUSION: These findings suggest that there are more activated T cells in decidua parietalis than in decidua basalis. Further investigation into differences between the two decidual sites may expand our understanding of the immunology of the maternal-fetal interface.