Human Th1 and Th2 cells: functional properties, regulation of development and role in autoimmunity

Evidence has accumulated suggesting the existence in humans of polarized T helper (Th) cell subsets, coded as Th1 and Th2, with defined cytokine secretion profiles. Immune responses to intracellular bacteria and viruses result in the preferential development of the Th1 cell subset. Th1 cells express cytolytic activity against antigen-presenting cells and provide helper function for IgM, IgG and IgA synthesis only at low T/B cell ratios. In contrast, Th2 cells develop in response to allergens or helminth antigens, provide help for all immunoglobulin classes, including IgE, and lack cytolytic potential. The cytokine milieu in the microenvironment plays a fundamental role in determining the functional phenotype of the subsequent antigen-specific Th1 or Th2 responses. In recent years it has become clear that Th1 and Th2 cells play different roles not only in protection against exogenous offending agents, but also immunopathology. Th2 cells are involved in immunopathology induced by helminths and are responsible for the initiation and maintenance of allergic disorders. Th1 cells seem to be involved in contact dermatitis, acute allograft rejection and organ-specific autoimmunity, such as thyroid autoimmune disorders, diabetes mellitus or multiple sclerosis, whereas less polarized patterns of Th cells are detectable in target organs of patients with rheumatoid arthritis. Sjogren's syndrome or systemic lupus erythematosus

Preferential expression of CD30 by human CD4+ T cells producing Th2-type cytokines

A large panel of human CD4+ T helper (Th) cell clones with established Th1, Th2, or Th0 profiles of cytokine secretion were examined for the expression of CD30, a member of the tumor necrosis factor receptor superfamily. Th1 clones expressed poor or no CD30 mRNA, and showed low or undetectable expression of both membrane and soluble CD30 (sCD30) protein, whereas Th2 clones showed both CD30 mRNA and membrane CD30 and released substantial amounts of sCD30. Th0 clones exhibited an intermediate pattern of CD30 expression and release. When T cells from the same donor were stimulated with three different antigens (purified protein derivative, PPD; Toxocara canis excretory/secretory antigen, TES; Lolium perenne group I, Lol p I), production of high concentrations of IFN-gamma, but not expression of CD30 or production of IL-4 and IL-5, were observed at any time after stimulation with PPD. In contrast, both CD30 expression and production of IL-4 and IL-5, but not of IFN-gamma, were concomitantly detectable in TES- and Lol p I-reactive T cells, suggesting a temporal relationship between CD30 expression and beginning of Th2-type cytokine production. Finally, CD4+CD30+ T cells specific for Lol p I and inducible to production of Th2-type cytokines were sorted out from the circulation of grass-sensitive patients in concomitance with the onset of allergic symptoms during the seasonal exposure to grass pollen. Thus, CD30 expression appears to be associated with the differentiation/activation pathway of human T cells producing Th2-type cytokines

Effect of subchronic in vivo exposure to nitrogen dioxide on lung tissue inflammation, airway microvascular leakage, and in vitro bronchial muscle responsiveness in rats.

OBJECTIVES: In a previous study on bronchoalveolar lavage fluid from rats exposed in vivo for seven days to 10 ppm nitrogen dioxide (NO2), it has been shown that there is an influx of macrophages into the airways. The present study investigated the effect of seven day exposure to 10 ppm NO2, on: (a) lung tissue inflammation and morphology; (b) airway microvascular leakage; (c) in vitro contractile response of main bronchi. METHODS: Lung tissue was studied by light microscopy, after fixing the lungs by inflation with 4% formalin at a pressure of 20 cm H2O. Microvascular leakage was measured by extravasation of Evans blue dye in the larynx, trachea, main bronchi, and intrapulmonary airways. Smooth muscle responsiveness was evaluated by concentration-responses curves to acetylcholine (10(-9)-10(-3) M), serotonin (10(-9)-10(-4) M), and voltage-response curves (12-28 V) to electrical field stimulation. RESULTS: Histology showed an increased total inflammation at the level of respiratory bronchioles and alveoli. No influx of inflammatory cells was found in the main bronchi. A loss of cilia in the epithelium of small airways and ectasia of alveolar capillaries was also found. By contrast, no alterations to microvascular permeability or modification of bronchial smooth muscle responsiveness was found. CONCLUSIONS: Subchronic exposure to 10 ppm NO2 causes airway inflammation and structural damage, but does not cause any persistent alteration to microvascular permeability or bronchial smooth muscle responsiveness in rats

Effect of subchronic in vivo exposure to nitrogen dioxide on lung tissue inflammation, airway microvascular leakage, and in vitro bronchial muscle responsiveness in rats

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Effect of subchronic in vivo exposure to nitrogen dioxide on lung tissue inflammation, airway microvascular leakage, and in vitro bronchial muscle responsiveness in rats.

OBJECTIVES: In a previous study on bronchoalveolar lavage fluid from rats exposed in vivo for seven days to 10 ppm nitrogen dioxide (NO2), it has been shown that there is an influx of macrophages into the airways. The present study investigated the effect of seven day exposure to 10 ppm NO2, on: (a) lung tissue inflammation and morphology; (b) airway microvascular leakage; (c) in vitro contractile response of main bronchi. METHODS: Lung tissue was studied by light microscopy, after fixing the lungs by inflation with 4% formalin at a pressure of 20 cm H2O. Microvascular leakage was measured by extravasation of Evans blue dye in the larynx, trachea, main bronchi, and intrapulmonary airways. Smooth muscle responsiveness was evaluated by concentration-responses curves to acetylcholine (10(-9)-10(-3) M), serotonin (10(-9)-10(-4) M), and voltage-response curves (12-28 V) to electrical field stimulation. RESULTS: Histology showed an increased total inflammation at the level of respiratory bronchioles and alveoli. No influx of inflammatory cells was found in the main bronchi. A loss of cilia in the epithelium of small airways and ectasia of alveolar capillaries was also found. By contrast, no alterations to microvascular permeability or modification of bronchial smooth muscle responsiveness was found. CONCLUSIONS: Subchronic exposure to 10 ppm NO2 causes airway inflammation and structural damage, but does not cause any persistent alteration to microvascular permeability or bronchial smooth muscle responsiveness in rats