FLOW CYTOMETRIC DETECTION OF TYPE 1 (IL-2, IFN-γ) AND TYPE 2 (IL-4, IL-5) CYTOKINES IN T-HELPER AND T-SUPPRESSOR/CYTOTOXIC CELLS IN RHEUMATOID ARTHRITIS, ALLERGIC ASTHMA AND ATOPIC DERMATITIS

Cytokine ◽  
1999 ◽  
Vol 11 (10) ◽  
pp. 783-788 ◽  
Author(s):  
A.J. Schuerwegh ◽  
L.S. De Clerck ◽  
L. De Schutter ◽  
C.H. Bridts ◽  
A. Verbruggen ◽  
...  
Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1618-1625
Author(s):  
Jérôme Estaquier ◽  
Jean Claude Ameisen

T-helper type-1 (Th1) and type-2 (Th2) cytokines, respectively, favor T-cell–mediated immunity and defense against intracellular pathogens or antibody-mediated immunity and defense against extracellular pathogens. Here we report that type-1 and type-2 cytokines also exert a regulatory effect on human monocyte survival. Interleukin-12 (IL-12) enhanced survival in long-term (10 days) cultures of adherent monocytes, whereas IL-10 induced death by apoptosis. In short-term cultures (2 days), the Th2 cytokines, IL-10 and IL-4, enhanced apoptosis; however, the Th1 cytokines, IL-12 and IL-2 only showed a reducing effect on monocyte apoptosis in culture conditions that decreased monocyte adhesion leading to increased levels of spontaneous apoptosis; finally, the Th1 cytokine, interferon-γ (IFN-γ), acted in a dose-dependent fashion: At high concentrations, IFN-γ enhanced apoptosis, which is an effect related to IL-10 secretion and reduced by antibodies to IL-10. Th1 cytokines reduced monocyte apoptosis induced by several stimuli: IL-2 reduced apoptosis induced by either IL-10 or high concentrations of IFN-γ, IL-12 reduced apoptosis induced by either the ligation of the Fas (CD95) molecule or γ-irradiation, and IFN-γ (at low doses that did not trigger apoptosis) reduced apoptosis induced by γ-irradiation. These findings suggest that the regulatory role of type-1 and type-2 cytokines on the development of immune responses and inflammatory reactions also involves the regulation of monocyte death by apoptosis.


2000 ◽  
Vol 191 (5) ◽  
pp. 847-858 ◽  
Author(s):  
Ryuta Nishikomori ◽  
Rolf O. Ehrhardt ◽  
Warren Strober

The differentiation of CD4+ T cells into T helper type 1 (Th1) cells is driven by interleukin (IL)-12 through the IL-12 receptor β2 (IL-12Rβ2) chain, whereas differentiation into Th2 cells is driven by IL-4, which downregulates IL-12Rβ2 chain. We reexamined such differentiation using IL-12Rβ2 chain transgenic mice. We found that CD4+ T cells from such mice were able to differentiate into Th2 cells when primed with IL-4 or IL-4 plus IL-12. In the latter case, the presence of IL-4 suppressed interferon (IFN)-γ production 10–100-fold compared with cells cultured in IL-12 alone. Finally, in studies of the ability of IL-12 to convert Th2 cells bearing a competent IL-12R to the Th1 cells, we showed that: (a) T cells bearing the IL-12Rβ2 chain transgene and primed under Th2 conditions could not be converted to Th1 cells by repeated restimulation under Th1 conditions; and (b) established Th2 clones transfected with the IL-12Rβ2 chain construct continued to produce IL-4 when cultured with IL-12. These studies show that IL-4–driven Th2 differentiation can occur in the presence of persistent IL-12 signaling and that IL-4 inhibits IFN-γ production under these circumstances. They also show that established Th2 cells cannot be converted to Th1 cells via IL-12 signaling.


Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1618-1625 ◽  
Author(s):  
Jérôme Estaquier ◽  
Jean Claude Ameisen

Abstract T-helper type-1 (Th1) and type-2 (Th2) cytokines, respectively, favor T-cell–mediated immunity and defense against intracellular pathogens or antibody-mediated immunity and defense against extracellular pathogens. Here we report that type-1 and type-2 cytokines also exert a regulatory effect on human monocyte survival. Interleukin-12 (IL-12) enhanced survival in long-term (10 days) cultures of adherent monocytes, whereas IL-10 induced death by apoptosis. In short-term cultures (2 days), the Th2 cytokines, IL-10 and IL-4, enhanced apoptosis; however, the Th1 cytokines, IL-12 and IL-2 only showed a reducing effect on monocyte apoptosis in culture conditions that decreased monocyte adhesion leading to increased levels of spontaneous apoptosis; finally, the Th1 cytokine, interferon-γ (IFN-γ), acted in a dose-dependent fashion: At high concentrations, IFN-γ enhanced apoptosis, which is an effect related to IL-10 secretion and reduced by antibodies to IL-10. Th1 cytokines reduced monocyte apoptosis induced by several stimuli: IL-2 reduced apoptosis induced by either IL-10 or high concentrations of IFN-γ, IL-12 reduced apoptosis induced by either the ligation of the Fas (CD95) molecule or γ-irradiation, and IFN-γ (at low doses that did not trigger apoptosis) reduced apoptosis induced by γ-irradiation. These findings suggest that the regulatory role of type-1 and type-2 cytokines on the development of immune responses and inflammatory reactions also involves the regulation of monocyte death by apoptosis.


Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 111
Author(s):  
Chien-Liang Chao ◽  
Hsin-Wen Huang ◽  
Muh-Hwan Su ◽  
Hang-Ching Lin ◽  
Wen-Mein Wu

Poria cocos (Schwein) F.A. Wolf (syn. Wolfiporia cocos) dried sclerotium, called fuling, is an edible, saprophytic fungus commonly used as a tonic and anti-aging traditional Chinese medicine. It is traditionally used in combination with other traditional Chinese medicines to enhance immunity. This study showed that P. cocos extract (Lipucan®) containing lanostane triterpenoids has no immunotoxicity and enhances non-specific (innate) immunity though activating natural killer cells and promotes interferon γ (IFN-γ) secretion by Type 1 T-helper (Th1) cells immune response. In addition, P. cocos extract significantly decreased interleukin (IL-4 and IL-5) secretion by Type 2 T-helper (Th2) cells immune response, which are related to the allergy response. The purified lanostane triterpenoids were first identified as active ingredients of P. cocos with enhanced non-specific immunity by promoting interferon γ (IFN-γ) secretion in a preliminary study. Our findings support that the P. cocos extract plays beneficial roles in immunoregulatory activity.


1999 ◽  
Vol 73 (4) ◽  
pp. 3292-3300 ◽  
Author(s):  
Ernst J. Verschoor ◽  
Petra Mooij ◽  
Herman Oostermeijer ◽  
Mike van der Kolk ◽  
Peter ten Haaft ◽  
...  

ABSTRACT The kinetics of T-helper immune responses generated in 16 mature outbred rhesus monkeys (Macaca mulatta) within a 10-month period by three different human immunodeficiency virus type 1 (HIV-1) vaccine strategies were compared. Immune responses to monomeric recombinant gp120SF2 (rgp120) when the protein was expressed in vivo by DNA immunization or when it was delivered as a subunit protein vaccine formulated either with the MF59 adjuvant or by incorporation into immune-stimulating complexes (ISCOMs) were compared. Virus-neutralizing antibodies (NA) against HIV-1SF2 reached similar titers in the two rgp120SF2 protein-immunized groups, but the responses showed different kinetics, while NA were delayed and their levels were low in the DNA-immunized animals. Antigen-specific gamma interferon (IFN-γ) T-helper (type 1-like) responses were detected in the DNA-immunized group, but only after the fourth immunization, and the rgp120/MF59 group generated both IFN-γ and interleukin-4 (IL-4) (type 2-like) responses that appeared after the third immunization. In contrast, rgp120/ISCOM-immunized animals rapidly developed marked IL-2, IFN-γ (type 1-like), and IL-4 responses that peaked after the second immunization. To determine which type of immune responses correlated with protection from infection, all animals were challenged intravenously with 50 50% infective doses of a rhesus cell-propagated, in vivo-titrated stock of a chimeric simian immunodeficiency virus-HIVSF13 construct. Protection was observed in the two groups receiving the rgp120 subunit vaccines. Half of the animals in the ISCOM group were completely protected from infection. In other subunit vaccinees there was evidence by multiple assays that virus detected at 2 weeks postchallenge was effectively cleared. Early induction of potent type 1- as well as type 2-like T-helper responses induced the most-effective immunity.


2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Joanna Salomon ◽  
Łukasz Matusiak ◽  
Danuta Nowicka-Suszko ◽  
Jacek C Szepietowski

Chitinase-3-like protein 1 (YKL-40) is suggested to be associated with type 2 T helper response and atopy. The aim of the study was the evaluation of serum YKL-40 level in atopic dermatitis. The study was performed on 59 patients: 27 males and 32 females, aged from 18 to 64 years. The severity of the disease was assessed by the SCORAD and objective SCORAD indexes. The severity of pruritus was measured by the visual analogue scale. Blood samples were taken to examine serum level of YKL-40, total IgE level, C-reactive protein level, white blood cell count, and neutrophil count. YKL-40 serum levels were significantly higher in patients with atopic dermatitis compared to the controls. There was a positive correlation between YKL-40 concentration and SCORAD, objective SCORAD, and pruritus. This study has shown that YKL-40 serum level is increased in patients with atopic dermatitis and reflects the severity of symptoms.


2001 ◽  
Vol 69 (10) ◽  
pp. 6064-6073 ◽  
Author(s):  
Cinzia Retini ◽  
Thomas R. Kozel ◽  
Donatella Pietrella ◽  
Claudia Monari ◽  
Francesco Bistoni ◽  
...  

ABSTRACT We previously demonstrated that the principal component of capsular material of Cryptococcus neoformans, glucuronoxylomannan (GXM), induces interleukin-10 (IL-10) secretion from human monocytes. Here we report that encapsulation of the yeast with GXM is able to down-regulate interleukin-12 (IL-12) production by monocytes that would normally occur in the absence of encapsulation. This phenomenon appeared to be the result of inhibition of the phagocytic process by encapsulation with GXM as well as of negative signals such as IL-10 secretion produced by interaction of GXM with leukocytes. Decreased secretion of IL-12 correlated with decreased release of gamma interferon (IFN-γ) from T cells, suggesting a role for encapsulation with GXM in hindering a T helper type 1 (Th1) response. This is supported by the ability of encapsulation with GXM to limit increased expression of B7-1 costimulatory molecules that otherwise might limit IL-10 secretion. Endogenous IL-10 played a critical role in modulatory activity associated with encapsulation with GXM. Blocking IL-10 with monoclonal antibody to IL-10 resulted in increased (i) IL-12 secretion, (ii) IFN-γ release from T cells, and (iii) killing of C. neoformans by monocytes. These results suggest that encapsulation with GXM limits development of a protective Th1-type response, an inhibitory process in which IL-10 plays a critical role. Scavengers of GXM and/or IL-10 could be useful in a protective Th1-type response in patients with cryptococcosis.


2016 ◽  
Vol 17 (1) ◽  
pp. 3-8 ◽  
Author(s):  
Milica Borovcanin ◽  
Ivan Jovanovic ◽  
Slavica Djukic Dejanovic ◽  
Gordana Radosavljevic ◽  
Nebojsa Arsenijevic ◽  
...  

AbstractThe phenomenological uniqueness of each patient with schizophrenia is determined by complex symptomatology, particularly the overlapping of symptoms and their prominence in certain phases of this mental disorder. Establishing biological markers is an important step in the further objectivisation and quantification of schizophrenia. Identifying the cytokine profiles that precede a psychotic episode could direct the strategies for relapse prevention and be useful in predicting disease progression and treatment response. In the context of infl ammation, TGF-β exerts potent anti-inflammatory and immunosuppressive functions by inhibiting pro-inflammatory cytokine synthesis, but it can also have pro-inflammatory functions through its stimulatory effects on inflammatory Th17 cells. It has been shown that the T helper cell type-1 and type-17 responses are reduced and type-2 response is increased in patients with schizophrenia. Both data from the literature and our results also indicate the presence of an anti-inflammatory response through production of the TGF-β regulatory cytokine. A meta-analysis of plasma cytokine alterations suggested that TGF-β is the state marker for acute exacerbation of schizophrenia, and we showed that TGF-β can also be a valuable marker for psychosis. Hyperactivity of TGF-β signalling pathways in schizophrenia may be both a neuroprotective mechanism and a possible therapeutic target.


2006 ◽  
Vol 203 (6) ◽  
pp. 1493-1505 ◽  
Author(s):  
Fuping Zhang ◽  
Mark Boothby

Transcriptional competence of the interferon-γ (IFN-γ) locus is enhanced as Th1 effectors develop from naive CD4 T lymphocytes; conversely, this gene is repressed during Th2 differentiation. We now show that the Switch (Swi)–sucrose nonfermenter (SNF) component Brahma-related gene 1 (Brg1) is recruited, and positioned nucleosomes are remodeled, in a Th1-specific manner that is dependent on the transcription factor Stat4 and calcineurin phosphatase activity. Interference with specific components of mammalian Swi–SNF complexes decreased CD4 T cell differentiation into IFN-γ–positive Th1 cells. These findings reveal a collaborative mechanism of IFN-γ gene regulation during Th1 differentiation and suggest that a Th1-specific chromatin structure is created by early recruitment of Swi–SNF complexes and nucleosome remodeling dependent on Stat4 and calcineurin activation.


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