scholarly journals Expression of Cd28 and Cd86 by Human Eosinophils and Role in the Secretion of Type 1 Cytokines (Interleukin 2 and Interferon γ)

1999 ◽  
Vol 190 (4) ◽  
pp. 487-496 ◽  
Author(s):  
Gaëtane Woerly ◽  
Nadine Roger ◽  
Sylvie Loiseau ◽  
David Dombrowicz ◽  
André Capron ◽  
...  

Eosinophils are the source of various immunoregulatory cytokines, but the membrane molecules involved in their secretion have not been clearly identified. Here we show that peripheral blood eosinophils from hypereosinophilic patients could express membrane CD86 but not CD80. The T cell costimulatory molecule CD28 is also detected on the eosinophil surface. CD28 ligation but not CD86 ligation resulted in interleukin (IL)-2 and interferon (IFN)-γ secretion by eosinophils, whereas IL-4, IL-5, and IL-10 were not detected. In contrast to T cells requiring two signals for effective stimulation, CD28 ligation alone was sufficient for optimal eosinophil activation. Eosinophil-derived IL-2 and IFN-γ were biologically active, as supernatants from anti-CD28–treated cells were able to induce CTLL-2 proliferation and major histocompatibility complex class II expression on the colon carcinoma cell line Colo 205, respectively. Addition of secretory immunoglobulin (Ig)A–anti-IgA complexes, which could induce the release of IL-10, very significantly inhibited both CD28-mediated IL-2 and IFN-γ release. These results suggest that the release of type 1 (IFN-γ and IL-2) versus type 2 cytokines by eosinophils is not only differential but also dependent on cross-regulatory signals. They confirm that through activation of costimulatory molecules, eosinophils could function as an immunoregulatory cell involved in the release of both type 1 and type 2 cytokines.

1999 ◽  
Vol 6 (1) ◽  
pp. 79-84 ◽  
Author(s):  
Bang-Ning Lee ◽  
Madeleine Duvic ◽  
Chih-Kwang Tang ◽  
Carlos Bueso-Ramos ◽  
Zeev Estrov ◽  
...  

ABSTRACT Mycosis fungoides (MF) and Sezary syndrome (SS) are the two main clinical entities of cutaneous T-cell lymphoma (CTCL). As the disease progresses from MF to SS, a switch from a type 1 (interleukin [IL]-2 and gamma interferon [IFN-γ]) to a type 2 (IL-4) cytokine production profile occurs. Although roles for type 1 and type 2 cytokines in the pathogenesis of CTCL have been proposed, the cellular origins of these cytokines are unclear. Using flow cytometry to identify individual T-cell subsets, we studied cytokine synthesis by the T cells of 13 patients with SS and 12 with MF and 9 hematologically healthy donors. Upon activation with phorbol 12-myristate 13-acetate (PMA), the numbers of T cells synthesizing IL-2 were similar for all study groups. Whereas the predominant T-cell producing IL-2 in healthy donors and in those with MF was CD7+, in patients with SS, it was CD7−. Although the number of IL-4+CD4+ T cells was low for all study groups, there was a significantly higher number of IL-4+ CD8+ T cells in patients with MF than in those with SS or healthy donors. There was a decline in the number of IFN-γ-producing T cells in CTCL donors compared to that in healthy donors. More importantly, there was a significant decrease in the number of IFN-γ-producing T cells with disease progression from MF to SS. The inability of these T cells to synthesize IFN-γ may have prognostic value in CTCL, since it may be responsible for the progression of the disease from MF to SS.


1999 ◽  
Vol 6 (4) ◽  
pp. 471-478 ◽  
Author(s):  
R. Harley ◽  
C. R. Helps ◽  
D. A. Harbour ◽  
T. J. Gruffydd-Jones ◽  
M. J. Day

ABSTRACT Semiquantitative reverse transcription-PCR assays were developed to measure feline interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-10, and IL-12 (p35 & p40); gamma interferon (IFN-γ); and glyceraldehyde-3-phosphate dehydrogenase mRNA concentrations in biopsies of feline oral mucosa. Biopsies were collected from 30 cats with chronic gingivostomatitis (diseased) prior to each cat receiving one of four treatments. In 23 cases replicate biopsies were collected 3 months after treatment commenced. Biopsies were also analyzed from 11 cats without clinical disease (nondiseased). Expression of IL-2, IL-10, IL-12 (p35 and p40), and IFN-γ was detected in most nondiseased biopsies, while IL-6 was detected in a minority, and IL-4 and IL-5 were both undetectable. Compared to nondiseased cats, the diseased population showed a significant increase in the relative mRNA expression of IL-2, IL-4, IL-6, IL-10, IL-12 (p35 and p40), and IFN-γ. In contrast, IL-5 mRNA expression was unchanged and was only detected in one case. No significant relationship was demonstrable between the change in relative expression of specific cytokine mRNA and the change in clinical severity of the local mucosal lesions over the treatment period. The results demonstrate that the normal feline oral mucosa is biased towards a predominantly (Th) type 1 profile of cytokine expression and that during the development of lesions seen in feline chronic gingivostomatitis there is a shift in the cytokine profile from a type 1 to a mixed type 1 and type 2 response.


Blood ◽  
2002 ◽  
Vol 99 (4) ◽  
pp. 1273-1281 ◽  
Author(s):  
Matthew J. Loza ◽  
Loris Zamai ◽  
Livio Azzoni ◽  
Emanuela Rosati ◽  
Bice Perussia

To determine whether production of type 1 and type 2 cytokines defines discrete stages of natural killer (NK) cell differentiation, cytokine expression was analyzed in human NK cells generated in vitro in the presence of interleukin-15 (IL-15) and/or IL-2 from umbilical cord blood hematopoietic progenitors. Like peripheral NK cells, the CD161+/CD56+ NK cells from these cultures contained a tumor necrosis factor alpha (TNF-α)+/granulocyte macrophage–colony-stimulating factor (GM-CSF)+ subset, an interferon gamma (IFN-γ)+ subset, mostly included within the former, and very few IFN-γ−/IL-13+ cells. Instead, most immature CD161+/CD56− NK cells, detectable only in the cultures with IL-2, produced IL-13, TNF-α, and GM-CSF, but not IFN-γ, and contained an IL-5+ subset. In short-term cultures with IL-12 and feeder cells, a proportion of the immature cells acquired the ability to produce IFN-γ. Part of these produced both IFN-γ and IL-13, irrespective of induced CD56 expression. These in vitro data indicate that ability to produce the type 2 cytokines IL-13 and IL-5 defines CD161+ NK cells at intermediate stages of differentiation, and is lost upon terminal functional differentiation, concomitant with acquired ability to produce IFN-γ.


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.


2003 ◽  
Vol 71 (1) ◽  
pp. 465-473 ◽  
Author(s):  
Francesca Sisto ◽  
Annarita Miluzio ◽  
Orazio Leopardi ◽  
Maurizio Mirra ◽  
Johan R. Boelaert ◽  
...  

ABSTRACT Penicillium marneffei is an intracellular opportunistic fungus causing invasive mycosis in AIDS patients. T cells and macrophages are important for protection in vivo. However, the role of T-cell cytokines in the immune response against P. marneffei is still unknown. We studied by semiquantitative reverse transcription-PCR and biological assays the patterns of expression of Th1 and Th2 cytokines in the organs of wild-type (wt) and gamma interferon (IFN-γ) knockout (GKO) mice infected intravenously with P. marneffei conidia. At 3 × 105 conidia/mouse, a self-limiting infection developed in wt BALB/c mice, whereas all GKO mice died at day 18 postinoculation. Splenic and hepatic granulomas were present in wt mice, whereas disorganized masses of macrophages and yeast cells were detected in GKO mice. The infection resolved faster in the spleens than in the livers of wt mice and was associated with the local expression of type 1 cytokines (high levels of interleukin-12 [IL-12] and IFN-γ) but not type 2 cytokines (low levels of IL-4 and IL-10). Conversely, both type 1 and type 2 cytokines were detected in the livers of wt animals. Disregulation of the cytokine profile was seen in the spleens but not in the livers of GKO mice. The inducible nitric oxide synthase mRNA level was low and the TNF-α level was high in both spleens and livers of GKO mice compared to wt mice. These data suggest that the polarization of a protective type 1 immune response against P. marneffei is regulated at the level of individual organs and that the absence of IFN-γ is crucial for the activation of fungicidal macrophages and the development of granulomas.


2020 ◽  
pp. 1-2
Author(s):  
Aheed Khan ◽  
Aanchal Sawhney

Tuberculosis (TB) is known to persist as latent infection and it is during this latent phase that the bacilli are able to bypass the host immunity and infect extrapulmonary sites such as lymph nodes. This study aims to find the tentative role of the cytokines released by type-1 and type-2 helper lymphocytes in patients of tuberculous lymphadenitis and understand their role and prevalence during immune response against MTB in these patients. Thirty patients with clinically diagnosed and cytologically proven Tuberculous lymphadenitis constituted the cases. Blood sample of 30 cases and 10 healthy volunteers was collected after obtaining written consent and the separated serum was stored at -80°C. ELISA was carried out using the standard method with the serum of these patients for Th-1 cytokines (IL-2 & interferon-γ) and for Th-2 cytokines (IL-4 and IL-5). The concentrations of the type-1 cytokines, especially INF- γ as well as type-2 cytokines, i.e IL-4 and IL-5 was highly increased in the patients selected. It was also noted that the levels of all the cytokines were increased if the patient had necrosis or AFB positive report on fine needle aspiration as compared to granuloma only report. Patients having tubercular lymphadenopathy show increased INF- γ in the circulation. It was also noted that IL-4 and IL-5 also seem to increase in proportion to the decreased immune status.


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.


Blood ◽  
2004 ◽  
Vol 103 (7) ◽  
pp. 2645-2647 ◽  
Author(s):  
Fotios P. Panitsas ◽  
Maria Theodoropoulou ◽  
Alexandra Kouraklis ◽  
Marina Karakantza ◽  
Georgios L. Theodorou ◽  
...  

Abstract Derangement of cellular immunity is central in the pathophysiology of adult autoimmune/idiopathic thrombocytopenic purpura (ITP). Herein we investigated cytokine gene expression in peripheral blood mononuclear cells (PBMCs) of adult chronic ITP patients and attempted to correlate cytokine polarization with the degree of thrombocytopenia. We used semiquantitative reverse-transcriptase–polymerase chain reaction (RT-PCR) to measure the expression of type-1 (interleukin-2 [IL-2], interferon γ [IFN-γ]) and type-2 (IL-4, IL-5, IL-10, IL-3, IL-13) cytokines by PBMCs from 21 patients and 11 controls. Plasma transforming growth factor β1 (TGF-β1) levels were measured by enzyme-linked immunoassay (ELISA). T helper 1 (Th1)/Th2 ([IL-2 + IFN-γ]/[IL-4 + IL-5]) cytokine mRNA ratios, thought to reflect the Th deviation of the pathogenic disease-specific T cells, and type-1/type-2 mRNA ratios, thought to reflect the overall immune response polarization, were significantly increased in ITP patients. The Th1/Th2 ratio was inversely correlated with platelet counts. TGF-β1 levels appeared suppressed in patients with active disease, though not significantly. Our findings show a clear type-1 cytokine polarization of the autoimmune response in adult ITP that persists irrespective of disease status.


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.


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