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Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS) mediated by autoreactive lymphocytes. The role of autoreactive lymphocytes in the CNS demyelination is well described, whereas very little is known about their role in remyelination during MS remission. In this study, we identified a new subpopulation of myelin-specific CD49d + CD154 + lymphocytes presented in the peripheral blood of MS patients during remission, that proliferated in vitro in response to myelin peptides. These lymphocytes possessed the unique ability to migrate towards maturing oligodendrocyte precursor cells (OPCs) and synthetize proinflammatory chemokines/cytokines. The co-culture of maturing OPCs with myelin-specific CD49d + CD154 + lymphocytes was characterized by the increase in proinflammatory chemokine/cytokine secretion that was not only a result of their cumulative effect of what OPCs and CD49d + CD154 + lymphocytes produced alone. Moreover, maturing OPCs exposed to exogenous myelin peptides managed to induce CD40-CD154-dependent CD49d + CD154 + lymphocyte proliferation. We confirmed, in vivo, the presence of CD49d + CD154 + cells close to maturating OPCs and remyelinating plaque during disease remission in the MS mouse model (C57Bl/6 mice immunized with MOG 3 5 - 55 ) by immunohistochemistry. Three weeks after an acute phase of experimental autoimmune encephalomyelitis, CD49d + /CD154 + cells were found to be co-localized with O4 + cells (oligodendrocyte progenitors) in the areas of remyelination identified by myelin basic protein (MBP) labelling. These data suggested that myelin-specific CD49d + CD154 + lymphocytes present in the brain can interfere with remyelination mediated by oligodendrocytes probably as a result of establishing proinflammatory environment., Competing Interests: The authors declare no conflict of interest.

The critical aspect in multiple sclerosis (MS) progression involves insufficient regeneration of CNS resulting from deficient myelin synthesis by newly generated oligodendrocytes (OLs). Although many studies have focused on the role of autoreactive lymphocytes in the inflammatory-induced axonal loss, the problem of insufficient remyelination and disease progression is still unsolved. To determine the effect of myelin-specific lymphocytes on OL function in MS patients and in a mouse model of MS, we cultured myelin induced MS CD49d + CD154 + circulating lymphocytes as well as Experimental Autoimmune Encephalomyelitis (EAE) mouse brain-derived T and memory B cells with maturing oligodendrocyte precursor cells (OPCs). We found that myelin-specific CD49d + CD154 + lymphocytes affected OPC maturation toward formation of immune reactive OLs. Newly generated OLs were characterized by imbalanced myelin basic protein (MBP) and proteolipid protein (PLP) production as well as proinflammatory chemokine/cytokine synthesis. The analysis of cellular pathways responsible for OL reprogramming revealed that CD49d + CD154 + lymphocytes affected miRNA synthesis by dysregulation of polymerase II activity. miR-665 and ELL3 turned out to be the main targets of MS myelin-specific lymphocytes. Neutralization of high intracellular miR-665 concentration restored miRNA and MBP/PLP synthesis. Together, these data point to new targets for therapeutic intervention promoting CNS remyelination.

Potent and broadly neutralizing antibodies (bnAbs) are the hallmark of HIV-1 protection by vaccination. The membrane-proximal external region (MPER) of the HIV-1 gp41 fusion protein is targeted by the most broadly reactive HIV-1 neutralizing antibodies. Here, we examine the structural and molecular mechansims of neutralization by anti-MPER bnAb, LN01, which was isolated from lymph-node-derived germinal center B cells of an elite controller and exhibits broad neutralization breadth. LN01 engages both MPER and the transmembrane (TM) region, which together form a continuous helix in complex with LN01. The tilted TM orientation allows LN01 to interact simultaneously with the peptidic component of the MPER epitope and membrane via two specific lipid binding sites of the antibody paratope. Although LN01 carries a high load of somatic mutations, most key residues interacting with the MPER epitope and lipids are germline encoded, lending support for the LN01 epitope as a candidate for lineage-based vaccine development., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Several studies demonstrated a relevant role of polymorphisms located within the HLA-B and -C loci and the Killer Immunoglobulin Receptors (KIRs) 3DL1 and 3DS1 in controlling HIV-1 replication. KIRs are regulatory receptors expressed at the surface of NK and CD8+ T-cells that specifically bind HLA-A and -B alleles belonging to the Bw4 supratype and all the -C alleles expressing the C1 or C2 supratype. We here disclose a novel signature associated with the Elite Controller but not with the long-term nonprogressor status concerning 2DS activating KIRs and HLA-C2 alleles insensitive to miRNA148a regulation. Overall, our findings support a crucial role of NK cells in the control of HIV-1 viremia.

N-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6) are crucial for the prevention of lung cancer. PUFAs may act through alteration of membrane fluidity and cell surface receptor functions; modulation of cyclooxygenase activity; and increased cellular oxidative stress, which may induce apoptosis and autophagy. Therefore the aim of the study was to investigate whether EPA and DHA (25-100 μM) are able to reduce human lung cancer cell growth through oxidative stress influence on autophagy and apoptosis. It was found that both EPA and DHA in the concentration-dependent manner suppressed the cell viability, enhanced cell death, induced activation of caspase-3/7 and potentiated intracellular oxidative DNA and protein damage. In response to PUFAs intracellular autophagic vacuolization occurred and the observed effect was reverted when the autophagy inhibitor 3-methyladenine (3-MA) was applied. The inhibition of the autophagic process enhanced the cell viability, suppressed cell death, and decreased activation of caspase-3/7 indicating that EPA and DHA-induced autophagy amplified A549 apoptotic cell death., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In normal and tumor cells, polyunsaturated fatty acids (PUFAs) act as intracellular second messengers, which play a role in signaling, proliferation and cell death. PUFAs have selective tumoricidal action and may alter sensitivity of tumor cells to cisplatin (CDDP), a commonly used anticancer agent. The aim of this study was to evaluate the influence of arachidonic acid (AA, 20:4 n-6), eicosapentaenoic acid (EPA, 20:5 n-3), docosahexaenoic acid (DHA, 22:6 n-3) and CDDP on autophagy and apoptosis in A549 human lung adenocarcinoma cells. Viability of A549 cells treated with CDDP and PUFAs was measured using the XTT tetrazolium salt based assay. Caspase-3/7 activity was estimated using ApoTox-Glo kit (Promega). Autophagic vac- uoles were detected by Cyto-ID Autophagy Detection Kit (Enzo). The results were compared to control cultures maintained in the absence of CDDP and PUFAs. PUFAs, in particular EPA and DHA, added to the cultivation medium, increased the antitumor activity of CDDP in A549 cells in a concentration dependent manner. In case of AA this effect was observed at the highest of the concentrations tested only (100 μM). Both, EPA and DHA, but not AA, significantly increased the amount of autophagic vacuoles and induced caspase-3/7 activity. The obtained results suggest that the antiproliferative effect of CDDP in A549 cells can be enhanced by AA and in particular by EPA and DHA through their influence on autophagic and apoptotic cell death. It is likely that BPA and DHA incorporated to the tumor cells may improve outcomes in lung cancer patients.

Genistein is a natural compound which occurs in Asian diet, rich in soy products. It has a wide spectrum of activity, expressed both in protecting cells from malignant transformation, reducing proliferation of tumor cells and stimulating apoptosis. In the other hand, genistein also prevents from some of the side effects manifesting in menopausal estrogen deficiency also being a good research object in this field. It has been shown, among others effect of genistein on: the level of free radicals and reactive oxygen species in the body, the metabolism of carcinogenic factors, cell cycle progression, initiation of apoptosis, angiogenesis, inflammatory processes and immune response. To achieve the desired therapeutic effect it is crucial to determine genistein dose titration in order to obtain an appropriate concentration in the tissues of phytohormone and duration of therapy.

The present study aimed to evaluate the role of genetic polymorphisms in the emergence of lipoatrophy or lipodystrophy in HIV-infected patients with antiretroviral therapy (ART) in Thailand. Position 455 upstream of the Apolipoprotein C3 gene (ApoC3 T-455C, rs2854116), codon 64 of the Beta3 adrenergic receptor gene (ARβ3 Tcod64C, rs4994), and position 670 upstream of the Fas gene (Fas A-670G, rs1800682) were genotyped in 829 HIV-infected Thai patients who had started ART. Crude and adjusted incidence rate ratios (IRR) were calculated using Poisson regression. The serum levels of cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were also analyzed. Multivariate analysis revealed an association between the Fas -670AA genotype, but not the ApoC3 -455 or ARβ3 cod64 genotypes, with the incidence of lipoatrophy after adjusting for gender and stavudine (d4T)-containing regimens (IRR=1.72, 95% CI=1.20-2.45, p=0.003). However, ApoC3 -455C homozygous patients showed elevated serum levels of triglycerides, while this genotype did not affect serum total cholesterol, HDL, or LDL levels in patients with lipoatrophy or lipodystrophy. In contrast, the ARβ3 cod64 genotype did not show any significant association with the serum levels of cholesterol, triglycerides, HDL, or LDL. In conclusion, Fas -670AA affected the incidence of lipoatrophy in HIV-1-infected Thai patients, while the ApoC3 -455C allele affected the serum levels of triglycerides. These results confirmed the role of genetics in the development of ART-related metabolic disorders.

Objective: The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a widespread, man-made, persistent organic pollutant with high immunotoxic potentials. It suppresses cell-mediated and humoral immune responses through mechanisms dependent on aryl-hydrocarbon receptor expression and immunosuppressive activity of the cells. Most sensitive to TCDD are organisms during fetal and infant life, mostly due to the developmental stage of many biological systems of the host, including immune system. Recent data show that T regulatory cells that have the potential to suppress immune reactions and which develop after TCDD exposure are also responsible for protection from allergy development. Our goal was to investigate if perinatal exposure to TCDD can affect allergic sensitisation and if T reg cells participate in this phenomenon., Materials and Methods: Mice, Balb/c, were perinatally exposed to TCDD or to the carrier. Six weeks old control or exposed mice were sensitised with ovalbumin. Spleen cells of the animals were used to assess the content of T reg cells by means of flow cytometry. Levels of cytokines were assessed by ELISA technique in supernatants of the cells stimulated with anti-CD3 antibody. As a measure of sensitisation, total IgE and anti-OVA IgE were measured in serum of mice by ELISA method. To assess the function of T reg cells isolated from OVA-sensitised control or TCDD exposed animals we performed transfer studies., Results: Here we show that perinatal exposure to TCDD decreases allergic sensitisation and that this process is related to inhibition of IL-4 synthesis rather than suppression mediated by T regulatory cells., Conclusion: We hypothesise that dioxin exposure can be an important environmental modulator of immunological responses that participate in allergic reactions.

Objectives: To investigate immunological changes in lymph nodes based on expression of cell-specific receptors and cytokine expression profile and accompanying inflammatory reactions in lungs of mice treated with chemicals of known potentials to induce respiratory sensitization and those in which activity in this regard is unclear., Materials and Methods: On day 1 and 7, Balb/c mice received toluene-2,4-diisocyanate (TDI), trimellitic anhydride (TMA), 1-chloro-2,4-dinitrobenzene (DNCB), glutaraldehyde (GA), formaldehyde (FA), benzalkonium chloride (ChB) or vehicle. On day 14, they received a single intranasal instillation with the same chemical or vehicle. On day 15, auricular lymph nodes (LN) were excised and used for analyzes of T-, B-cells, expression of CD44 and for the estimation of IL-4 and IFN-gamma production after in vitro stimulation with concanavalin A (ConA) and also for IL-4 and IFN-gamma mRNA expression analyses using Real-Time PCR. Inflammatory changes in lungs were observed by estimation of TNF-alpha and MIP-2 concentrations and cell numbers and their type in BAL., Results: There were no significant changes in cell subpopulations of T helper cells in LN. The percent of B cells was significantly increased after treatment with DNCB, TDI, and GA. Increased expression of CD44 on T cells was also observed. Both IL-4 and IFN-gamma were found increased in TDI- and FA-treated mice, while only IL-4 was increased in TMA-treated mice. Real-Time PCR analyses, however, showed increased IL-4 mRNA expression for TDI- and TMA-, and IFN-gamma mRNA expression for DNCB-treated mice. We haven't observed significant changes in inflammatory reactions in the lungs of exposed animals., Conclusions: Studying immunological changes with first determining the activation status of T cells followed by analyzes of expression of mRNA for Th1 and Th2 cytokines in murine model could be a useful method for assessment of the potentials of chemicals to induce respiratory sensitization but is not sufficient. Addition of ventilatory measurements, but not necessarily inflammatory reactions, could complete the model.

The objective of the study was to characterize better the immunologic mechanisms underlying a previously developed animal model of chemical-induced asthma. BALB/c and severe combined immunodeficiency disease (SCID) mice received toluene diisocyanate (TDI) or vehicle on each ear on day 1 and/or day 7. On day 10, they were intranasally challenged with TDI or vehicle. Ventilatory function was monitored by whole body plethysmography for 40 min after challenge. Reactivity to methacholine was measured 23 h later: enhanced pause and actual resistance measurements. Pulmonary inflammation was assessed 1, 6, and 24 h after challenge by bronchoalveolar lavage (BAL). Tumor necrosis factor-alpha and macrophage inflammatory protein (MIP)-2 levels were measured in BAL. Immunological parameters included total IgE, IgG1, and IgG2a in serum, lymphocyte populations in auricular and cervical lymph nodes, and IL-4 and IFN-gamma levels in supernatants of lymph node cells, cultured with or without concanavalin A. Ventilatory changes suggestive of airway obstruction and increased methacholine reactivity were observed in all TDI-sensitized and TDI intranasally instilled mice, except in SCID mice. A neutrophil influx, accompanied by an increase in MIP-2 levels, was found in BAL of all responding groups 6 and 24 h after intranasal challenge. In BALB/c mice an increased level of CD19+ B cells was found in the auricular lymph nodes. IL-4 and IFN-gamma levels were increased in supernatants of concanavalin A-stimulated auricular lymph node cells from BALB/c mice completely treated with TDI. These results indicate that our model is dependent on the presence of lymphocytes, but it is not characterized by a preferential stimulation of Th1 or Th2 lymphocytes.

Background: Occupational asthma can be caused by chemicals. Previously, we established a murine model of immunologically mediated chemical-induced asthma using toluene diisocyanate., Objective: We sought to verify this model using trimellitic anhydride (TMA), a respiratory sensitizer, and 1-chloro-2,4-dinitrobenzene (DNCB), a dermal sensitizer., Methods: BALB/c mice received dermal applications (vehicle or chemical) on days 1 and 7. On day 10, they received an intranasal instillation (vehicle or chemical). Whole-body plethysmography (enhanced pause) was used to monitor changes in ventilatory function and methacholine reactivity. Pulmonary inflammation was assessed by using bronchoalveolar lavage (cells, TNF-alpha levels, and macrophage inflammatory protein 2 levels). Immunologic parameters included total serum IgE levels, lymphocyte distribution in auricular and cervical lymph nodes, and IL-4 and IFN-gamma levels in supernatants of lymph node cells incubated with or without concanavalin A., Results: Mice dermally treated and intranasally challenged with TMA experienced markedly increased enhanced pause immediately after intranasal challenge and increased methacholine reactivity (24 hours later). Mice similarly treated with DNCB did not show any ventilatory changes. Neutrophil influx and increased macrophage inflammatory protein 2 and TNF-alpha levels were found in bronchoalveolar lavage fluid in both TMA- and DNCB-treated mice. The proportion of CD19+ B cells was increased in auricular and cervical lymph nodes of TMA-treated mice. IL-4 and IFN-gamma levels were increased in supernatants of concanavalin A-stimulated auricular and cervical lymph node cells of TMA- or DNCB-treated mice; however, the relative proportions of IL-4 and IFN-gamma levels differed between TMA- and DNCB-treated mice. Serum total IgE levels were increased in TMA-treated mice only., Conclusion: Both compounds induce a mixed T(H)1-T(H)2 response, but only TMA induced ventilatory changes., Clinical Implications: In the workplace avoiding skin contact with chemical sensitizers might be advised to prevent chemical-induced asthma.

Objectives: The inspiration of cobalt containing dust leads to various respiratory symptoms, including asthma and interstitial lung disease. Occupational asthma caused by cobalt chloride has been diagnosed in a 35-year-old patient, who worked as a diamond polishing disc former. The patient presented a 2-year history of dyspnea, cough and symptoms of rhinitis., Materials and Methods: The patient underwent a medical history interview, skin prick tests with common and occupational allergens (cobalt and nickel chloride), and pulmonary function testing both before and after the nasal provocation with 0.05% cobalt chloride. Additionally, the authors analyzed morphological and biochemical changes before and after the specific nasal challenge test. Cell proliferation analysis was also carried out., Results: Skin prick tests (SPTs) with common environmental allergens were found to be negative, while SPTs with cobalt chloride were positive for all applied solutions. The provocation with cobalt chloride caused a significant increase in the proportion of eosinophils, basophils and albumin during the late allergic reaction. The positive lymphocyte transformation caused by cobalt was also observed., Conclusions: Cobalt salts may induce occupational asthma. The mechanism of this asthma may be IgE-mediated. The cobalt-sensitized lymphocytes may play an important role in this disease.

Occupational asthma is the principal cause of work-related respiratory disease in the industrial world. In the absence of satisfactory models for predicting the potential of low molecular weight chemicals to cause asthma, we verified that dermal sensitization prior to intranasal challenge influences the respiratory response using toluene diisocyanate (TDI), a known respiratory sensitizer. BALB/c mice received TDI or vehicle (acetone/olive oil) on each ear on three consecutive days (days 1, 2, and 3; 0.3 or 3% TDI) or only once (day 1, 1% TDI). On day 7, the mice received similar dermal applications of vehicle or the same concentration of TDI as before ("boost"). On day 10, they received an intranasal dose of TDI (0.1%) or vehicle. Ventilatory function was monitored by whole body plethysmography for 40 min after intranasal application, and reactivity to inhaled methacholine was assessed 24 h later. Pulmonary inflammation was assessed by bronchoalveolar lavage and histology. Mice that received an intranasal dose of TDI without having received a prior dermal application of TDI did not exhibit any ventilatory response or inflammatory changes compared to vehicle controls. In contrast, mice that had received prior application(s) of TDI, even if only on day 7, exhibited the following: ventilatory responses, compatible with bronchoconstriction, immediately after intranasal application with TDI; enhanced methacholine responsiveness 24 h later; and pulmonary inflammation characterized by neutrophils. This was, however, not the case in mice that received the highest dermal amount of TDI (3% on days 1, 2, and 3). These findings suggest that respiratory response to TDI depends on prior frequency and concentration of dermal sensitization in mice.

Clinical and basic mechanism observations reveal interactions between neural and immune systems. These two systems create a complex network for recognizing danger to the host and its protection from outside pathogenic elements as well as from inside overreactions of inflammatory character. Here, we review the interactions of these two systems in relation to the effects of pesticides that clearly involve elements of cholinergic lymphocytic system. We discuss cellular and soluble elements of the immune system, which may be affected by pesticide exposure. We suggest that in-depth studies of the influence of pesticides on lymphocytes may contribute to the development of sensitive methods of measuring early adverse effects appearing in response to pesticide exposure.

CD30 receptor has been known for almost 20 years, but its expression and activity are still the subject of many investigations. Its expression was found in different malignancies, and most of the studies regarding CD30 focus on its role in lymphomas. The progress that has already been made in this field is reflected in implementation of CD30 as a target for immunotoxin, which has been tested in phase I study in treating Hodgkin lymphoma. CD30 is present also on normal, activated T cells of all cytokine profiles. However, increased density of CD30 and CD30-mediated Th2 cytokine production provide evidence of its role in determining the activity of T cells toward synthesis of cytokines and involvement in reactions of Th2 characteristics. Pleiotropic signaling mediated by CD30 does not implicate this receptor just as a cytokine costimulator; it proves to be important in several different activities of T cells.

Interest in CD30 has mainly focused on its ability to discriminate between T helper (Th)2 and Th1 subpopulations. The role of CD30 as the marker for Th2 cells is still controversial, which may be due to the fact that the expression and the role of CD30 is not fully understood. The data presented in this paper provides information on the expression and activity of CD30 in T cell lines specific to allergen or tuberculin-purified protein derivative (PPD) as the model of Th2 or Th1 responses, respectively. The results have shown that CD30 expression was the highest on T cells stimulated with antigen in the presence of interleukin (IL)-12 and it was present on both cell lines, regardless of antigen specificity. Activation of the CD30 receptor on CD4+ T cells, however, showed differences in mRNA expression for IL-4 between these cells. IL-4 mRNA was induced by CD30 costimulation at the same level as was obtained with anti-CD28 agonistic antibodies in allergen-specific T cells. In PPD-specific T cells this effect was not observed. Additionally, there was no effect of anti-CD30 stimulation on IL-6 mRNA expression in any of the cell lines. Comparison of protein cytokine levels for IL-4 and interferon (IFN)-gamma have shown that the highest production of IL-4 was obtained from allergen-specific T cells costimulated with anti-CD28. Although this effect was much lower in the case of CD30 costimulation, it was still above that of anti-CD3 activation alone. No effect of CD30 activation was observed in regard to IFN-gamma mRNA or protein expression in any cell line. The results of the study showed that the CD30 receptor is not exclusively present on Th2 cells; however, its activity may promote a Th2-dependent reaction by modulating IL-4 production.

The most recent evidence suggests that the immune system responses are not regulated only by the presence of antigens but they are also influenced by the brain and behavior. It has been known for some time that stressful conditions alter the functioning of the immune system. Despite methodological difficulties in the quantitation of stress, and its association with the onset of illness, the concept of the stress impact on susceptibility to several diseases is widely acknowledged. This paper reviews the effects of stress on the endocrine and central nervous systems and presents the interactions between these systems and the immune response after exposure to stress signals.

In the inductive phase of contact allergic dermatitis, simple chemical compounds (haptens) produce together with epidermic proteins adducts presented by Langerhans cells to T lymphocytes. Binding to protein carrier is a necessary condition of transforming a low-molecular allergen into immunogenic one and evoking immunological reaction. The production of allergen adducts with proteins is conditioned by the presence of electrophilic groups in their molecules, or their acquiring during biotransformation phase I. Active allergen metabolites undergo further alterations during biotransformation phase II which leads most frequently to the decline in their chemical activity and more rapid excretion from the body. The number of reactive metabolites (reactive allergens) available for producing adducts with proteins keeps the balance between activation and deactivation reactions. Glutathione S-transferases play a particular role in the allergens (or their metabolites) deactivation process in biotransformation phase II. These enzymes catalyse reactions responsible for the declined electrophilic potential of allergens (or their metabolites), and thus for the decrease in the number of allergen molecules able to produce protein covalent bindings (adducts). Glutathione S-transferases, occurring in the human cellular cytoplasm belong to five classes: alpha(GST A), mu(GST M), theta(GST P), pi(GST T) and Z(GST Z), as well as to one class present in microsomes. The study indicated the presence of isoenzymes GST T1 and GST M1 in the skin. Both isoforms participate in the process of low-molecular allergen biotransformation. Carriers of defective genes GST T1 and/or GST M1 are more vulnerable to allergenic effect of some allergens, e.g. thimerosal, which is associated with the absence of or decrease in the activity of isoenzymes GST T1 and GST M1.

Background: The alpha(4) integrin, as alpha(4)beta(1) (VLA-4) or alpha(4)beta(7), is critical for T cell migration and proliferation, although its functional modulation remains poorly understood. We hypothesized that increased receptor density, based on new receptor chain synthesis, was one such mechanism. We examined the surface receptor density of the alpha(4) and beta(1) chains on CD4+CD45RO+ cells, and the mRNA expression of these and the beta(7) chain in response to allergen and nonallergen antigen stimulation., Methods: Flow-cytometric analyses for CD49d, CD29, and CD45RO were performed on T cell lines specific for timothy, tetanus, and Candida from atopic and nonatopic donors. RNA was extracted from cells sorted to select CD4+/CD49d-positive cells before and after stimulation. Equivalent amounts of cDNA for beta-actin, alpha(4), beta(1) and beta(7) were used in PCR, and the products were quantified using phosphoimaging., Results: CD49d expression is heterogeneous on T cell lines and is upregulated by antigen stimulation on CD4+ T cells. The surface expression on CD4+CD45RO+ timothy allergen or tetanus toxoid T cell lines is at least double that found on CD45RO- cells. Antigen stimulation upregulated CD49d expression on the CD4+CD45RO+ subpopulation of both cell lines although it was not as significant as in the case of all CD4+ T cells. CD29 surface expression behaves similarly. Candida had no effect on CD49d or CD29. Messenger RNA expression for the alpha(4) chain (CD49d) is significantly upregulated 48 h following the addition of timothy or tetanus. beta(7) chain expression also rises significantly on both cell lines. beta(1) chain expression increases, but not significantly., Conclusions: The surface expression of the CD49d is heterogeneous and much higher on CD4+CD45RO+ cells than on CD4+RO- T cells. The CD49d integrin chain on CD4+ T cells is upregulated following antigen exposure. However, the CD4+CD45RO+ subpopulation is only partially responsible for this increase suggesting other T cells to have this receptor expression upregulated. CD29 expression behaves similarly. Messenger RNA expression increases coordinately for alpha(4), beta(7), and not significantly for beta(1) in these cells. These observations provide a potential mechanism for the selective accumulation of T cells at sites of inflammation, and suggest an important point of intervention for allergic and inflammatory disease., (Copyright 2000 S. Karger AG, Basel)

T cell receptor, accessory molecules, cytokines are important regulatory factors that determine the development and function of T lymphocytes. Among them are also molecules belonging to superfamily of tumor necrosis factor receptor (TNFR) which beside CD30 include CD27, CD40, TNFR-I and -II, Fas (CD95), OX40, 4-1BB (CDw137), nerve growth factor receptor, lymphotoxin-beta receptor, Apo3/DR3/Ws1-1/lymphocyte associated receptor of death, DR4, DR5/TNF-related apoptosis-inducing ligand, osteoprotegerin, and TNFR-related 2. CD30 recognized originally on Reed-Sternberg cells of Hodgkin's lymphoma became of interest in studies of Th1 and Th2 cell differentiation. This paper shows recent findings regarding CD30 expression and its pleiotropic role in T cell function. It provides information about controversial role of CD30 as Th2 cell differentiation marker and gives concise insight into the function of this receptor as a signal transducing molecule.

The alpha4 chain (CD49d), which constitutes one of the chains of alpha4beta1 (very late activating antigen-4 [VLA-4]) and alpha4beta7 integrins, mediates migration of T cells to extravascular spaces. The interaction between VLA-4 and vascular cell adhesion molecule-1 (VCAM-1) has been shown to be the critical pathway for the selective accumulation of eosinophils and basophils at sites of allergic inflammation. T lymphocytes are also specifically recruited into allergic sites, including the allergic asthmatic airway. Increased numbers of activated CD4+ cells expressing the DR antigen subset of the human leukocyte antigens (HLA-DR) appear in the allergic lung 48 h after allergen inhalation. The mechanisms by which these cells localize into the lung are still unknown. We report that stimulation of allergen-specific T cells with allergen in vitro resulted in enhanced expression of alpha4 chain (CD49d) as measured by receptor density on allergen-specific T-cell lines and T-cell clones. Kinetic studies showed that CD49d density was enhanced over a 24- to 48-h period in a time-dependent fashion, and was coordinately upregulated with HLA-DR expression. We also demonstrated that increased expression of CD49d on T-cell lines 24 h and 48 h after stimulation correlated with increased adhesion to the CS-1 fragment of fibronectin. In contrast, lymphocyte function-associated antigen-1b (LFA-1b) (CD11b), LFA-3 (CD58), and intercellular adhesion molecule-1 (ICAM-1) (CD54) expression did not change with allergen stimulation. We also showed that CD49d receptor density on T cells obtained by bronchoalveolar lavage (BAL) of allergic patients before and 48 h after allergen challenge was significantly higher than that on T cells taken from BAL of normal subjects and from controls with other inflammatory lung diseases. Taken together, these findings indicate that allergen stimulation activates allergen-specific T cells and coordinately induces increased CD49d receptor expression and binding to counterligands. We postulate that allergen-driven upregulation of CD49d, which together with the beta1 chain constitutes VLA-4 integrin, may be responsible for the selective accumulation of T cells in the allergic asthmatic lung.

The effect of formaldehyde exposure on the sensitization of mice to ovalbumin was investigated. Significantly increased IgE antiovalbumin titers were found in mice sensitized intranasally to ovalbumin and exposed for 10 days to 2 mg/m3 of formaldehyde. In contrast, mice not exposed to formaldehyde or exposed once a week produced low levels of this antibody. The exposure of mice, sensitized intraperitoneally with ovalbumin, to formaldehyde did not increase sensitization. It was concluded that formaldehyde facilitates sensitization of mice to ovalbumin by changes that occur in the respiratory tract.

13 formaldehyde-sensitive contact dermatitis patients and 5 healthy subjects were exposed to formaldehyde (FM) at a concentration 0.5 mg/m3, in an exposure chamber for 2 hours. There was no significant decrease of the ventilatory parameters either in healthy subjects or in contact dermatitis patients following the exposure Bronchial hyperreactivity to histamine (PC20) increased in one healthy and two patients with contact dermatitis. Neutrophils were isolated from whole venous blood before the test and 30 minutes and 24 hours after the exposure. All subjects with allergic contact dermatitis had chemiluminescence higher before the FM provocation in a comparison with the healthy ones. It increased significantly 30 minutes post the exposure and was much higher 24 hours after the exposure in the comparison with the neutrophil chemiluminescence before the test.

Environmental pollutants seem to be responsible for dramatical increase of allergic disorders that have been observed lately. The best documented environmental factors facilitating allergy development are: ozone, diesel-exhaust particulate matter and tobacco smoke. Formaldehyde and SO2 seem to be also very important but still are not sufficiently documented. Mechanisms involved in allergy promotion include: better penetration of allergens across respiratory mucosa or direct modulation of immunological response.

This paper indicates some immunological aspects of asbestos-related diseases and especially concerns the activity of macrophages--cells of immunological surveillance. Macrophages establish a very important population of cells which initiate or suppress specific immune response; they are responsible for effective T-cell activation, express antitumour activity. The process of lung fibrosis generated by the inhalation and deposition of asbestos fibres is also closely related to macrophage activity. An open question which is still to be resolved concerns asbestos-induced fibrosis; it may arise as a consequence of tissue injury and repair or change collagen synthesis. Another question is, to what extent macrophages may be protective cells and when they become undesirable? Since their overstimulation or damage in the case of chronic exposure to asbestos dust may be the reason of the increased release of inflammatory mediators, reactive oxygen intermediates which may in turn cause tissue injury, fibrosis or, in final effect, cancer. If so, we could then say that lung response (expressed by e.g. alveolar macrophage activity) to chemical insult may cause further damage to this tissue.