scholarly journals T helper 1 to T helper 2 shift in cytokine expression: an autoregulatory process in superantigen-associated psoriasis progression?

2009 ◽  
Vol 58 (2) ◽  
pp. 180-184 ◽  
Author(s):  
Sarika Jain ◽  
Iqbal R. Kaur ◽  
Shukla Das ◽  
S. N. Bhattacharya ◽  
Anjani Singh
Keyword(s):  
Interleukin 2 ◽  
Cytokine Expression ◽  
T Helper ◽  
T Helper 1 ◽  
Th2 Response ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Duration Of Disease ◽  
Th1 Immune Responses

Psoriasis is an inflammatory skin disorder characterized by increased activation of CD4+ T lymphocytes, and systemic and local overexpression of pro-inflammatory cytokines such as interleukin 2 (IL-2), gamma interferon (IFN-γ), IL-6 and tumour necrosis factor alpha, indicating that immunopathogenesis of the disease is T helper 1 (Th1) mediated. Several studies suggest a pivotal role of bacterial superantigens in the initiation and/or exacerbation of this illness. This study was conducted to assess the systemic Th1/Th2 imbalance in Indian psoriasis patients presenting with variable duration of disease by studying systemic superantigen-stimulated peripheral blood mononuclear cell (PBMC) cytokine expression. PBMCs were isolated and stimulated in vitro with superantigens (streptococcal pyrogenic exotoxin A and staphylococcal enterotoxin B), and the cytokines released (IFN-γ for a Th1 response, and IL-4 and IL-10 for a Th2 response) were assayed. In contrast to controls, psoriasis patients in the early course of disease were characterized by significantly increased expression of the pro-inflammatory cytokine IFN-γ, whilst a shift towards IL-10 secretion (Th2 response) was observed in those presenting with increased duration of disease. These observations suggest a possible shift from a Th1 to a Th2 cytokine response with superantigen-associated progression for the duration of psoriasis, perhaps as an adaptive process by the immune system in an attempt to downregulate abnormal inflammatory Th1 immune responses.

scholarly journals Cytokine Production in Cell Culture by Peripheral Blood Mononuclear Cells from Immunocompetent Hosts

1998 ◽  
Vol 5 (1) ◽  
pp. 78-81 ◽  
Author(s):  
Rohit K. Katial ◽  
Doris Sachanandani ◽  
Carolyn Pinney ◽  
Michael M. Lieberman
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Pokeweed Mitogen ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Blood Mononuclear Cells ◽  
Factor Alpha

ABSTRACT The production of interleukin 2 (IL-2) gamma interferon, IL-4, tumor necrosis factor alpha (TNF-α), TNF-β, IL-5, and IL-10 in vitro by peripheral blood mononuclear cells cultured from healthy immunocompetent subjects after mitogen stimulation was determined. The mitogens used were concanavalin A, phytohemagglutinin, pokeweed mitogen, and Staphylococcus aureus Cowen. The results obtained provide a normal range for the production of these cytokines under specified conditions in vitro.

scholarly journals Polyfunctional T Lymphocytes Are in the Peripheral Blood of Donors Naturally Immune to Coccidioidomycosis and Are Not Induced by Dendritic Cells

2009 ◽  
Vol 78 (1) ◽  
pp. 309-315 ◽  
Author(s):  
Lance Nesbit ◽  
Suzanne M. Johnson ◽  
Demosthenes Pappagianis ◽  
Neil M. Ampel
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
High Expression ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Ifn Γ

ABSTRACT Coccidioidomycosis is a fungal infection endemic in the southwestern United States that is increasing in incidence. While cellular immunity correlates with protection from clinical illness, the precise elements of that response are undefined. Using the coccidioidal antigen preparation T27K and multiparametric flow cytometry, the in vitro frequency of polyfunctional T lymphocytes in the peripheral blood of naturally immune healthy donors and those who were nonimmune was determined. Polyfunctional CD4 lymphocytes, defined as producing intracellular interleukin 2 (IL-2), gamma interferon (IFN-γ), and tumor necrosis factor alpha simultaneously, had a frequency of 137 per 400,000 events among peripheral blood mononuclear cells (PBMC) of immune donors compared to 11 per 400,000 PBMC from nonimmune donors (P = 0.03). When monocyte-derived mature dendritic cells pulsed with T27K (mDCT27K) were used for antigen presentation, the frequency of polyfunctional CD4 T lymphocytes did not significantly increase for either group, although mDCT27K did significantly increase the concentrations of IL-2 and IFN-γ released by PBMC from nonimmune donors (P = 0.02). After in vitro stimulation with T27K, polyfunctional CD4 and CD8 lymphocytes of PBMC from immune donors had a mixture of low- and high-expression CCR7 cells, suggesting both effector and central memory, compared with predominantly high-expression CCR7 cells when PBMC were incubated with the mitogen phytohemagglutinin (P = 0.03). These data demonstrate the presence of polyfunctional T lymphocytes in the peripheral blood of individuals with coccidioidal immunity and suggest a model for the in vitro testing of vaccine candidates for coccidioidomycosis.

scholarly journals Failure of Gamma Interferon but Not Interleukin-10 Expression in Response to Human Papillomavirus Type 11 E6 Protein in Respiratory Papillomatosis

2004 ◽  
Vol 11 (3) ◽  
pp. 538-547 ◽  
Author(s):  
James A. DeVoti ◽  
Bettie M. Steinberg ◽  
David W. Rosenthal ◽  
Lynda Hatam ◽  
Andrea Vambutas ◽  
...  
Keyword(s):  
T Cells ◽  
Human Papillomavirus ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Interleukin 2 ◽  
Cytokine Expression ◽  
Gamma Interferon ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

ABSTRACT Recurrent respiratory papillomatosis (RRP) is a chronic, debilitating disease of the upper airway caused by human papillomavirus type 6 (HPV-6) or HPV-11. We describe responses of peripheral blood mononuclear cells (PBMC) and T cells from RRP patients and controls to the HPV-11 early proteins E6 and E7. PBMC were exposed in vitro to purified E6 or E7 proteins or transduced with fusion proteins containing the first 11 amino acids of the human immunodeficiency virus type 1 protein tat fused to E6 or E7 (tat-E6/tat-E7). TH1-like (interleukin-2 [IL-2], gamma interferon [IFN-γ], IL-12, and IL-18), and TH2-like (IL-4 and IL-10) cytokine mRNAs were identified by reverse transcription-PCR, and IFN-γ and IL-10 cytokine-producing cells were identified by enzyme-linked immunospot assay. These studies show that HPV-11 E6 skews IL-10-IFN-γ expression by patients with RRP toward greater expression of IL-10 than of IFN-γ. In addition, there is a general cytokine hyporesponsiveness to E6 that is more prominent for TH1-like cytokine expression by patients with severe disease. Patients showed persistent IL-10 cytokine expression by the nonadherent fraction of PBMC when challenged with E6 and tat-E6, and, in contrast to controls, both T cells and non-T cells from patients expressed IL-10. However, E7/tat-E7 cytokine responses in patients with RRP were similar to those of the controls. In contrast, E6 inhibited IL-2 and IL-18 mRNA expression that would further contribute to a cytokine microenvironment unfavorable to HPV-specific, T-cell responses that should control persistent HPV infection. In summary, E6 is the dominant inducer of cytokine expression in RRP, and it induces a skewed expression of IL-10 compared to the expression of IFN-γ.

scholarly journals Consistent production of a higher TH1:TH2 cytokine ratio by stimulated T cells in men compared with women

2000 ◽  
pp. 31-36 ◽  
Author(s):  
JA Giron-Gonzalez ◽  
FJ Moral ◽  
J Elvira ◽  
D Garcia-Gil ◽  
F Guerrero ◽  
...  
Keyword(s):  
Sex Hormones ◽  
Interleukin 2 ◽  
Interleukin 10 ◽  
Lymphocyte Culture ◽  
Interleukin 4 ◽  
T Helper ◽  
T Helper 1 ◽  
In Vitro Effects ◽  
Culture Supernatants

OBJECTIVE: To evaluate the T helper 1 (T(H)1)/T helper 2 (T(H)2) lymphocyte cytokine profiles in women and men and to study the in vitro effects of sex hormones on lymphocyte secretion of cytokines. METHODS: Analysis of serum concentration and lymphocyte synthesis of T(H)1 (gamma interferon (INF-gamma) and interleukin 2 (IL-2)) and T(H)2 (interleukin 4 (IL-4) and interleukin 10 (IL-10)) cytokines was performed in 20 women and 15 men. Analysis of modifications in cytokine secretion induced by supplementation of lymphocyte culture with increasing concentrations of sex hormones was carried out. RESULTS: Higher levels of INF-gamma and IL-2 and lower levels of IL-4 and IL-10 were detected in the phytohemagglutinin-stimulated lymphocyte culture supernatants of men compared with women; the INF-gamma:IL-4 ratio was significantly higher in men. In women, similar concentrations of all the cytokines were detected in culture supernatants obtained during the follicular and the luteal phases. The addition of sex hormones did not modify the concentration of cytokines in supernatants of phytohemagglutinin-stimulated T-cell cultures. CONCLUSIONS: Women present a predominant T(H)2 cytokine profile, which could be involved in immune responses characterized principally by the secretion of antibodies. This could be a factor implicated in the higher concentration of immunoglobulins or the increased prevalence of autoimmune diseases detected in females.

scholarly journals Immune Response Induction and New Effector Mechanisms Possibly Involved in Protection Conferred by the Cuban Anti-Meningococcal BC Vaccine

2001 ◽  
Vol 69 (7) ◽  
pp. 4502-4508 ◽  
Author(s):  
Oliver Pérez ◽  
Miriam Lastre ◽  
José Lapinet ◽  
Gustavo Bracho ◽  
Miriam Dı́az ◽  
...  
Keyword(s):  
Immune Response ◽  
Mononuclear Cells ◽  
Adult Population ◽  
Interleukin 2 ◽  
Outer Membrane Vesicles ◽  
Delayed Type Hypersensitivity ◽  
T Helper 1 ◽  
Opsonic Activity ◽  
Peripheral Blood Mononuclear

ABSTRACT This report explores the participation of some afferent mechanisms in the immune response induced by the Cuban anti-meningococcal vaccine VA-MENGOC-BC. The induction of delayed-type hypersensitivity in nursing babies and lymphocyte proliferation after immunization is demonstrated. The presence of gamma interferon IFN-γ and interleukin-2 (IL-2) mRNAs but absence of IL-4, IL-5, and IL-10 mRNAs were observed in peripheral blood mononuclear cells from immunized subjects after in vitro challenge with outer membrane vesicles. In addition, some effector functions were also explored. The presence of opsonic activity was demonstrated in sera from vaccinees. The role of neutrophils as essential effector cells was shown. In conclusion, we have shown that, at least in the Cuban adult population, VA-MENGOC-BC induces mechanisms with a T-helper 1 pattern in the afferent and effector branches of the immune response.

Remission of Alopecia Universalis after 1 Year of Treatment with Dupilumab in a Patient with Severe Atopic Dermatitis

2021 ◽  
pp. 1-4
Author(s):  
Maurizio Romagnuolo ◽  
Mauro Barbareschi ◽  
Simona Tavecchio ◽  
Luisa Angileri ◽  
Silvia Mariel Ferrucci
Keyword(s):  
Atopic Dermatitis ◽  
Skin Disorder ◽  
Human Monoclonal Antibody ◽  
Severe Atopic Dermatitis ◽  
T Helper ◽  
T Helper 1 ◽  
Th2 Response ◽  
Alopecia Universalis ◽  
T Helper 2 ◽  
Relapsing Remitting

Alopecia areata (AA), an autoimmune disease with a relapsing-remitting course, represents the second cause of non­scarring alopecia worldwide and is associated with several comorbidities, notably atopic dermatitis (AD). In particular, AD is related to its more severe forms alopecia totalis (AT) and alopecia universalis (AU) [Nat Rev Dis Primers. 2017;3:17011]. Considering that AA has been classified as T helper 1-driven disease, whereas AD is the prototypical T helper 2 (Th2)-driven skin disorder, recent studies suggest that these forms may underlie a different chemokine expression resulting in a Th2 skewing as a key pathomechanism that could explain this association [JAMA Dermatol. 2015 May;151(5):522–8]. Several reports showed that dupilumab, a fully human monoclonal antibody targeting the interleukin 4α receptor and thus downregulating Th2 response, led to an improvement of AA associated with AD; most of these patients were females with AT or AU, early-onset AD, and atopic comorbidities [Exp Dermatol. 2020 Aug;29(8):726–32]. We report here a case to further support this hypothesis.

scholarly journals Anticancer immunity induced by a synthetic tumor-targeted CD137 agonist

2021 ◽  
Vol 9 (1) ◽  
pp. e001762
Author(s):  
Punit Upadhyaya ◽  
Johanna Lahdenranta ◽  
Kristen Hurov ◽  
Sailaja Battula ◽  
Rachel Dods ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Tumor Antigens ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Human Peripheral Blood ◽  
Interleukin 2 ◽  
Cancer Therapeutics ◽  
Peripheral Blood Mononuclear ◽  
Tnf Superfamily

BackgroundIn contrast to immune checkpoint inhibitors, the use of antibodies as agonists of immune costimulatory receptors as cancer therapeutics has largely failed. We sought to address this problem using a new class of modular synthetic drugs, termed tumor-targeted immune cell agonists (TICAs), based on constrained bicyclic peptides (Bicycles).MethodsPhage libraries displaying Bicycles were panned for binders against tumor necrosis factor (TNF) superfamily receptors CD137 and OX40, and tumor antigens EphA2, Nectin-4 and programmed death ligand 1. The CD137 and OX40 Bicycles were chemically conjugated to tumor antigen Bicycles with different linkers and stoichiometric ratios of binders to obtain a library of low molecular weight TICAs (MW <8 kDa). The TICAs were evaluated in a suite of in vitro and in vivo assays to characterize their pharmacology and mechanism of action.ResultsLinking Bicycles against costimulatory receptors (e.g., CD137) to Bicycles against tumor antigens (e.g., EphA2) created potent agonists that activated the receptors selectively in the presence of tumor cells expressing these antigens. An EphA2/CD137 TICA (BCY12491) efficiently costimulated human peripheral blood mononuclear cells in vitro in the presence of EphA2 expressing tumor cell lines as measured by the increased secretion of interferon γ and interleukin-2. Treatment of C57/Bl6 mice transgenic for the human CD137 extracellular domain (huCD137) bearing EphA2-expressing MC38 tumors with BCY12491 resulted in the infiltration of CD8+ T cells, elimination of tumors and generation of immunological memory. BCY12491 was cleared quickly from the circulation (plasma t1/2 in mice of 1–2 hr), yet intermittent dosing proved effective.ConclusionTumor target-dependent CD137 agonism using a novel chemical approach (TICAs) afforded elimination of tumors with only intermittent dosing suggesting potential for a wide therapeutic index in humans. This work unlocks a new path to effective cancer immunotherapy via agonism of TNF superfamily receptors.

Abstract 425: Lycopene Modulates T Lymphocyte Function by Modulating Th1 Responses and Treg Lymphocyte Population

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Lynsey M Mills ◽  
Heather Wilson ◽  
Frank Thies
Keyword(s):  
T Lymphocyte ◽  
T Regulatory Cells ◽  
Mononuclear Cells ◽  
T Cell Subsets ◽  
Lymphocyte Function ◽  
T Helper ◽  
T Helper 1 ◽  
Peripheral Blood Mononuclear ◽  
Lymphocyte Activity ◽  
Ifn Γ

Increased lycopene intake might have cardiovascular benefits, potentially through anti-inflammatory mechanisms. We recently showed that lycopene can influence lymphocyte activity by modulating processes involved in early cellular activation. T lymphocytes comprise different subsets, T cytotoxic, T helper 1 (Th1), T helper 2 (Th2) and T regulatory cells (Treg). We aimed to determine whether lycopene could specifically modulate T-cell subsets function and activity. Peripheral blood mononuclear cells from 11 healthy adults were cultured for 18hr to 60h in the presence of lycopene-enriched liposomes (0-1.18μg lycopene/ml) with or without mitogens. The secretion of cytokines representative of Th1,Th2 and Treg activities were measured by ELISA (IL-2, IL-1β, IL-10, IFN-γ and TGF-β) or cytometric bead array (IL-4, IL-10, IL17 and IFN-γ). The population profile of Tc (CD3+/CD8+), Th (CD3+/CD4+), Treg (CD4+/CD25+), and the Treg subsets nTreg (CD4+/CD25+/FoxP3+) and iTreg (CD4+/CD25+/IL-10+) was determined by flow cytometry. After 18h incubation, IL-2 concentration in the medium was significantly reduced (-29%, p=0.001) in the presence of lycopene (1.18μg/mL). Similar effects were observed after 36h and 60h culture for IFN-γ (-23%, p=0.015), Il-10 (-30%, p=0.023), IL-17 (-30%, p=0.019) but not IL-4 or TGF-β. The proportion of Treg cell was also significantly increased by 36% (p=0.001) in the presence of lycopene (1.18μg/mL) compared with non-treated activated cells. Furthermore, the proportions of iTreg cells were significantly increased by after incubation with lycopene while the proportion of nTreg cells decreased (-20.5 %, p=0.049). We conclude that increased lycopene intake may be beneficial against atherogenesis by modulating T lymphocyte function, particularly in relation toTh1 and Treg.

scholarly journals A 70-Kilodalton Recombinant Heat Shock Protein ofCandida albicans Is Highly Immunogenic and Enhances Systemic Murine Candidiasis

1998 ◽  
Vol 66 (5) ◽  
pp. 2154-2162 ◽  
Author(s):  
Carla Bromuro ◽  
Roberto La Valle ◽  
Silvia Sandini ◽  
Francesca Urbani ◽  
Clara M. Ausiello ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Mononuclear Cells ◽  
Cell Mediated Immunity ◽  
Healthy Human ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Ifn Γ

ABSTRACT The 70-kDa recombinant Candida albicans heat shock protein (CaHsp70) and its 21-kDa C-terminal and 28-kDa N-terminal fragments (CaHsp70-Cter and CaHsp70-Nter, respectively) were studied for their immunogenicity, including proinflammatory cytokine induction in vitro and in vivo, and protection in a murine model of hematogenous candidiasis. The whole protein and its two fragments were strong inducers of both antibody (Ab; immunoglobulin G1 [IgG1] and IgG2b were the prevalent isotypes) and cell-mediated immunity (CMI) responses in mice. CaHsp70 preparations were also recognized as CMI targets by peripheral blood mononuclear cells of healthy human subjects. Inoculation of CaHsp70 preparations into immunized mice induced rapid production of interleukin-6 (IL-6) and tumor necrosis factor alpha, peaking at 2 to 5 h and declining within 24 h. CaHsp70 and CaHsp70-Cter also induced gamma interferon (IFN-γ), IL-12, and IL-10 but not IL-4 production by CD4+ lymphocytes cocultured with splenic accessory cells from nonimmunized mice. In particular, the production of IFN-γ was equal if not superior to that induced in the same cells by whole, heat-inactivated fungal cells or the mitogenic lectin concanavalin A. In immunized mice, however, IL-4 but not IL-12 was produced in addition to IFN-γ upon in vitro stimulation of CD4+ cells with CaHsp70 and CaHsp70-Cter. These animals showed a decreased median survival time compared to nonimmunized mice, and their mortality was strictly associated with organ invasion by fungal hyphae. Their enhanced susceptibility was attributable to the immunization state, as it did not occur in congenitally athymic nude mice, which were unable to raise either Ab or CMI responses to CaHsp70 preparations. Together, our data demonstrate the elevated immunogenicity of CaHsp70, with which, however, no protection against but rather some enhancement of Candida infection seemed to occur in the mouse model used.

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