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Cell Cytokines (cell + cytokine)
Selected AbstractsA novel T cell cytokine, secreted osteoclastogenic factor of activated T cells, induces osteoclast formation in a RANKL-independent mannerARTHRITIS & RHEUMATISM, Issue 11 2009Leonard Rifas Objective Chronic T cell activation is central to the etiology of rheumatoid arthritis (RA), an inflammatory autoimmune disease that leads to severe focal bone erosions and generalized systemic osteoporosis. Previous studies have shown novel cytokine-like activities in medium containing activated T cells, characterized by potent induction of the osteoblastic production of interleukin-6 (IL-6), an inflammatory cytokine and stimulator of osteoclastogenesis, as well as induction of an activity that directly stimulates osteoclast formation in a manner independent of the key osteoclastogenic cytokine RANKL. This study was undertaken to identify the factors secreted by T cells that are responsible for these activities. Methods Human T cells were activated using anti-human CD3 and anti-human CD28 antibodies for 72 hours in AIM V serum-free medium to obtain T cell,conditioned medium, followed by concentration and fractionation of the medium by fast-protein liquid chromatography. Biologically active fractions were resolved using sodium dodecyl sulfate,polyacrylamide gel electrophoresis. Major bands were analyzed by mass spectrometry, and a major candidate protein was identified. This novel cytokine was cloned, and its expression was analyzed using recombinant DNA technologies. Results A single novel cytokine that could induce both osteoblastic IL-6 production and functional osteoclast formation in the absence of osteoblasts or RANKL and that was insensitive to the effects of the RANKL inhibitor osteoprotegerin was identified in the activated T cell,conditioned medium; this cytokine was designated secreted osteoclastogenic factor of activated T cells (SOFAT). Further analysis of SOFAT revealed that it was derived from an unusual messenger RNA splice variant coded by the threonine synthase,like 2 gene homolog, which is a conserved gene remnant coding for threonine synthase, an enzyme that functions only in microorganisms and plants. Conclusion SOFAT may act to exacerbate inflammation and/or bone turnover under inflammatory conditions such as RA or periodontitis and in conditions of estrogen deficiency. [source] Despite large-scale T cell activation, only a minor subset of T cells responding in vitro to Actinobacillus actinomycetemcomitans differentiate into effector T cellsJOURNAL OF PERIODONTAL RESEARCH, Issue 3 2000Homayoun H. Zadeh Recent studies in our laboratory have demonstrated that Actinobacillus actinomycetemcomitans has a potent T cell stimulatory effect, activating more than half of all T cells. However, since the fate of these activated T cells was not known, the present study sought to determine whether all of these T cells differentiate into effector cells. To that end, the intracellular expression of T cell cytokines (IL-2, IFN-,, IL-4 and IL-10) in response to A. actinomycetemcomitans was determined by flow cytometry. Results demonstrated a time-dependent increase in the expression of the cytokines, most reaching peak levels at 24,48 h. At 48 h, the proportion of T cells expressing each of the cytokines were as follows: IL-2 (1.7%±0.3), IFN-,(1.8%±0.5), IL-4 (1.0%±0.2) and IL-10 (1.5%±0.5). These data indicated that only 2,5% of all T cells stimulated with A. actinomycetemcomitans expressed any T cell cytokines. The finding of large-scale T cell activation in the absence of cytokine expression suggests that the activation of T cells in response to A. actinomycetemcomitans is incomplete. To investigate this phenomenon, peripheral blood mononuclear cells (PBMC) were cultured with A. actinomycetemcomitans for 24 h followed by sorting of the activated (CD69+) cells by immunomagnetic separation and restimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. Results demonstrated that nearly 90% of the T cells were unresponsive to further restimulation. A possible explanation for this unresponsiveness is the induction of clonal anergy among the responding T cells. To determine possible preferential effects of the stimulation on specific cytokines, the expression of each cytokine among T cells responding to A. actinomycetemcomitans was compared to the maximum levels achieved by PMA+ionomycin stimulation. Results showed that number of IL-2+ and IFN-,+ T cells observed in response to A. actinomycetemcomitans were between 2% and 7% of those seen in response to PMA+ionomycin. Conversely, the proportions of T cells expressing IL-4 or IL-10 were between 35% and 90% of those following stimulation with PMA+ionomycin. Hence, A. actinomycetemcomitans appears to more preferentially induce T cells [source] T Helper Cell Cytokine Profiles in Preterm LaborAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2004Lisa M. Hollier Problem:, To compare concentrations of T-helper cell cytokines in women with preterm labor (PTL) to normal pregnancies. Method of study:, Fourteen women with PTL and 13 women with normal pregnancies from 24 to 34 weeks were enrolled in this pilot study. Peripheral blood mononuclear cells (PBMCs) and cervical secretions were collected. PBMCs were cultured and stimulated with mitogens. Culture supernatants and cervical secretions were assayed for type 1 (interferon- ,, IL-12) and type 2 cytokines (IL-4, IL-5, IL-10 and IL-13) using enzyme-linked immunosorbent assays. Results:, There were no intergroup differences in median cytokine concentrations in PBMC cultures, or in ratios of type 1/type 2 cytokines. In cervical secretions, the median concentration of IL-4 was significantly higher in control patients. Conclusions:, PTL patients appeared to have an altered T-helper cytokine balance in cervical secretions. Further study of the role of cytokines produced in the adaptive response appears warranted. [source] 1,25-dihydroxyvitamin D3 modulates Th17 polarization and interleukin-22 expression by memory T cells from patients with early rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 1 2010E. M. Colin Objective To examine the immunologic mechanism by which 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) may prevent corticosteroid-induced osteoporosis in patients with early rheumatoid arthritis (RA), with a focus on T cell biology. Methods Peripheral blood mononuclear cells (PBMCs) and CD4+CD45RO+ (memory) and CD4+CD45RO, (non-memory) T cells separated by fluorescence-activated cell sorting (FACS) from treatment-naive patients with early RA were stimulated with anti-CD3/anti-CD28 in the absence or presence of various concentrations of 1,25(OH)2D3, dexamethasone (DEX), and 1,25(OH)2D3 and DEX combined. Levels of T cell cytokines were determined by enzyme-linked immunosorbent assay and flow cytometry. Results The presence of 1,25(OH)2D3 reduced interleukin-17A (IL-17A) and interferon-, levels and increased IL-4 levels in stimulated PBMCs from treatment-naive patients with early RA. In addition, 1,25(OH)2D3 had favorable effects on tumor necrosis factor , (TNF,):IL-4 and IL-17A:IL-4 ratios and prevented the unfavorable effects of DEX on these ratios. Enhanced percentages of IL-17A, and IL-22,expressing CD4+ T cells and IL-17A,expressing memory T cells were observed in PBMCs from treatment-naive patients with early RA as compared with healthy controls. Of note, we found no difference in the percentage of CD45RO+ and CD45RO, cells between these 2 groups. Interestingly, 1,25(OH)2D3, in contrast to DEX, directly modulated human Th17 polarization, accompanied by suppression of IL-17A, IL-17F, TNF,, and IL-22 production by memory T cells sorted by FACS from patients with early RA. Conclusion These data indicate that 1,25(OH)2D3 may contribute its bone-sparing effects in RA patients taking corticosteroids by the modulation of Th17 polarization, inhibition of Th17 cytokines, and stimulation of IL-4. [source] Relationship between changes in interferon-, production by peripheral blood T cells and changes in peak expiratory flow rate in patients with chronic stable asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2002Y. I. Koh Summary Background Cytokines production by T helper lymphocytes (Th cells), which orchestrate the interplay of the different cells involved in airway inflammation of asthma, may be reflected in peripheral blood. Some studies have suggested that the Th cell cytokines by peripheral blood T cells correlate with asthma severity. Objective To investigate the relationship between changes in IFN-, production by peripheral blood T cells and changes in lung function in chronic stable asthmatics. Methods Sixteen patients with chronic stable moderate asthma aged 35,65 years (nine women) were recruited. Morning and evening peak expiratory flow rates (PEFR) monitoring and blood sampling for peripheral blood T cell culture, total IgE and blood eosinophils were performed at baseline and week 12. Levels of IFN-,, IL-4 and IL-5 in culture supernatants of peripheral blood T cell were determined by using enzyme-linked immunosorbent assay (ELISA) kits. Results Patients with increased IFN-, changes from baseline showed significantly increased changes in morning (P = 0.02) and evening (P < 0.05) PEFR compared with those with decreased IFN-, changes. The changes in IFN-, production and IFN-,: IL-4 ratio significantly correlated with the changes in morning PEFR (Rs = 0.59, P < 0.02; Rs = 0.63, P < 0.01, respectively) and tended to correlate with the changes in evening PEFR (Rs = 0.45, P = 0.08; Rs = 0.5, P = 0.05, respectively). The changes in IL-4 and IL-5 did not correlate with the changes in IgE and blood eosinophils, respectively. Conclusions These findings suggest that IFN-, may be associated with the alteration of lung function in asthmatics and play a role in the pathophysiology of chronic stable asthma. [source] Differences in regulatory pathways identify subgroups of T cell-derived Th2 cytokinesCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2000K. Rafiq We analysed regulatory mechanisms involved in the production of Th2 cytokines by freshly isolated human T cells. We used an in vitro culture system in which the primary signal was provided by a cross-linking anti-CD3 MoAb presented on the Fc receptors of P815 cells. Both CD80 and CD86, expressed on transfected P815 cells, were able to provide efficient costimulation for the production of IL-4, IL-5 and IL-13. IL-2 was also highly important for induction of all three Th2 cytokines. However, differences between IL-4 on the one hand and IL-5 and IL-13 on the other hand were observed when sensitivity to cyclosporin A (CsA) was studied. CsA (an inhibitor of calcineurin phosphatase activity) strongly inhibited IL-4 production, but it did either not affect or even increased IL-5 and IL-13 production. In accordance with this, CD80 and phorbol myristate acetate (PMA) (without anti-CD3 or calcium ionophore) were sufficient to induce production of IL-5 and IL-13, but not of IL-4. The subgrouping of Th2 cytokines was further confirmed at another level on the basis of differences in cell sources: IL-4 was predominantly produced by CD4+ T cells, while IL-5 and IL-13 were produced by both CD4+ and CD8+ T cells. Thus, differences in cell sources and in the requirement of the calcium/calcineurin-signalling pathway allowed us to identify two subgroups (IL-4 and IL-5/IL-13) among human Th2-type T cell cytokines. [source] Cytokine detection in HIV-1/HHV-8 co-infected subjectsCELL BIOCHEMISTRY AND FUNCTION, Issue 3 2002Agostino Pugliese Abstract In a previous work we have evaluated some immunologic and haematologic parameters of HIV-1 positive subjects co-infected with HHV-8. A worsening of these values were generally described in these patients as compared with those HIV-1 positive, but negative for HHV-8. Now we have studied the influence of HHV-8 co-infection of HIV-1 positive subjects on the production of some cytokines to make clear the question of its role in the immuno-deregulation of the above-mentioned subjects. In particular we have analysed serum levels of IL-4 and IL-10, Th2 type T cells cytokines, IFN-,, an indirect marker of Th1 cells activation and IL-18, a cytokine produced by monocytic-macrophagic cells, which is able to induce IFN-, production and Th1 T lymphocytes activation. No significant differences were found as regards the IFN-, serum levels (92.1,±,24.3 pg ml,1 in the case of HIV-1 positive/HHV-8 negative subjects and 96.0,±,17.4 pg ml,1 in those HIV-1 positive/HHV-8 positive). In healthy subjects the mean level of this cytokine was 17.6,±,5.2 pg ml,1 (significant difference with both the former values at p,<,0.001). Moreover IL-4 and IL-10, which were undetectable in healthy individuals, showed the following values in HIV-1positive/HHV-8 negative subjects: 31.9,±,2.7 pg ml,1 and 119.8,±,85.1 pg ml,1 respectively and in HIV-1 positive/HHV-8 positive subjects: 30.4,±,4.8 pg ml,1 and 69.4,±,65.3 pg ml,1 (not significant differences). In contrast IL-18 reached a mean level of 1001.2,±,360.5 pg ml,1 in HIV-1 positive/HHV-8 negative subjects, but showed a significant reduction in HIV-1 positive/HHV-8 positive subjects (737.6,±,284.3 pg ml,1,p,<,0.05) and presented very low levels in healthy individuals (21.3,±,30.3 pg ml,1). Moreover a significant correlation (,0.984,p,<,0.001) was noticed between IL-18 reduction in HIV-1 positive subjects co-infected with HHV-8 and the degree of positivity of HHV-8. These data suggest that HHV-8 co-infection has no influence on the switch Th1, Th2 in HIV-1 positive subjects, but is able to reduce IL-18 production, useful for Th1 subset restoration. Copyright © 2002 John Wiley & Sons, Ltd. [source] | ||||||||||