scholarly journals Comparison of Serum and Cell-Specific Cytokines in Humans

2001 ◽  
Vol 8 (6) ◽  
pp. 1097-1103 ◽  
Author(s):  
Janine Jason ◽  
Lennox K. Archibald ◽  
Okey C. Nwanyanwu ◽  
Martha G. Byrd ◽  
Peter N. Kazembe ◽  
...  
Keyword(s):  
T Cells ◽  
Interleukin 2 ◽  
Peripheral Blood Cell ◽  
Necrosis Factor Alpha ◽  
Entire Study ◽  
Serum Cytokines ◽  
Tnf Α ◽  
Immunodeficiency Virus ◽  
Factor Alpha ◽  
Ifn Γ

ABSTRACT Cytokines function at the cellular, microenvironmental level, but human cytokine assessment is most commonly done at the macro level, by measuring serum cytokines. The relationships between serum and cellular cytokines, if there are any, are undefined. In a study of hospitalized patients in Malawi, we compared cytometrically assessed, cell-specific cytokine data to serum interleukin 2 (IL-2), IL-4, IL-6, IL-8, IL-10, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) levels in 16 children and 71 (IL-2, -4, -6, -10) or 159 (IL-8, IFN-γ, and TNF-α) adults, using Wilcoxon rank sum tests and Pearson's (rp ) and Spearman's (rs ) rank correlations. For the entire study group, correlations between identical serum and cellular cytokines mainly involved IL-8 and IFN-γ, were few, and were weakly positive (r < 0.40). Blood culture-positive persons had the most and strongest correlations, including those between serum IL-2 levels and the percentages of lymphocytes spontaneously making IL-2 (rs = +0.74), serum IL-8 levels and the percentages of lymphocytes spontaneously making IL-8 (rp = +0.66), and serum IL-10 levels and the percentages of CD8+ T cells making TNF-α (rp = +0.89). Human immunodeficiency virus (HIV)-positive persons had the next largest number of correlations, including several serum IL-8 level correlations, correlation of serum IL-10 levels with the percentages of lymphocytes producing induced IL-10 (rs = +0.36), and correlation of serum IFN-γ levels and the percentages of lymphocytes spontaneously making both IL-6 and IFN-γ in the same cell (rp = +0.59). HIV-negative, malaria smear-positive, and pediatric patients had few significant correlations; for the second and third of these subgroups, serum IL-8 level was correlated with the percentage of CD8− T cells producing induced IL-8 (rs = +0.40 and rs = +0.56, respectively). Thus, the strength of associations between serum and cellular cytokines varied with the presence or absence of bloodstream infection, HIV status, and perhaps other factors we did not assess. These results strongly suggest that serum cytokines at best only weakly reflect peripheral blood cell cytokine production and balances.

scholarly journals Invariant Vα14 Chain NKT Cells Promote Plasmodium berghei Circumsporozoite Protein-Specific Gamma Interferon- and Tumor Necrosis Factor Alpha-Producing CD8+ T Cells in the Liver after Poxvirus Vaccination of Mice

2005 ◽  
Vol 73 (2) ◽  
pp. 849-858 ◽  
Author(s):  
Simone Korten ◽  
Richard J. Anderson ◽  
Carolyn M. Hannan ◽  
Eric G. Sheu ◽  
Robert Sinden ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Plasmodium Berghei ◽  
Tumor Necrosis ◽  
Nkt Cells ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Understanding the protective mechanism in the liver induced by recombinant vaccines against the pre-erythrocytic stages of malaria is important for vaccine development. Most studies in mice have focused on splenic and peripheral blood T cells and identified gamma interferon (IFN-γ)-producing CD8+ T cells as correlates of protection, which can be induced by prime-boost vaccination with recombinant poxviruses. Invariant natural killer T (Vα14iNKT) cells can also protect against liver stage malaria, when activated, and are abundant in the liver. Since poxviruses have nonspecific immunomodulating effects, which are incompletely understood, we investigated whether recombinant poxviruses affect the protective properties of hepatic Vα14iNKT cells and thus vaccine efficacy. We show that intradermal vaccination with recombinant poxviruses activated Vα14iNKT cells and NK cells in the livers of BALB/c mice while inducing IFN-γ- and tumor necrosis factor alpha (TNF-α)-producing pre-erythrocytic stage antigen-specific CD8+ T cells. Greater numbers of hepatic Vα14iNKT cells secreted interleukin-4 than IFN-γ. Vaccinated Vα14iNKT-cell-deficient mice had lower, but still protective levels of hepatic and splenic IFN-γ+ and TNF-α+ CD8+ T cells and better protection rates later after challenge with Plasmodium berghei sporozoites. Therefore, vaccine-activated hepatic Vα14iNKT cells help in generating specific T cells but are not required for protection induced by recombinant poxviruses. Furthermore, double-positive INF-γ+/TNF-α+ CD8+ T cells were enriched in protected livers, suggesting that cells expressing both of these cytokines may be most relevant for protection.

scholarly journals Human Immunodeficiency Virus Type 1 Controllers but Not Noncontrollers Maintain CD4 T Cells Coexpressing Three Cytokines

2007 ◽  
Vol 81 (21) ◽  
pp. 12071-12076 ◽  
Author(s):  
Sunil Kannanganat ◽  
Bill G. Kapogiannis ◽  
Chris Ibegbu ◽  
Lakshmi Chennareddi ◽  
Paul Goepfert ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Cd4 T Cells ◽  
Strong Association ◽  
Interleukin 2 ◽  
Inverse Correlation ◽  
Necrosis Factor Alpha ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
And Control

ABSTRACT Here, we evaluate the cytokine coexpression profiles of human immunodeficiency virus (HIV)-specific CD4 T cells for the expression of the cytokines gamma interferon (IFN-γ), interleukin-2, and tumor necrosis factor alpha. In controllers, CD4 T cells producing three or two cytokines (triple producers and double producers, respectively) represented >50% of the total response. In contrast, in noncontrollers ∼75% of responding cells produced only one cytokine (single producers), mostly IFN-γ. Cells producing three cytokines were functionally superior to those producing single cytokines and showed an inverse correlation (P < 0.001) with viral load. These results demonstrate a strong association between the maintenance of highly functional CD4 T cells producing three cytokines and control of HIV-1.

scholarly journals Th1 Cytokines Are Essential for Placental Immunity to Listeria monocytogenes

2005 ◽  
Vol 73 (10) ◽  
pp. 6322-6331 ◽  
Author(s):  
Ellen M. Barber ◽  
Melissa Fazzari ◽  
Jeffrey W. Pollard
Keyword(s):  
T Cells ◽  
Listeria Monocytogenes ◽  
Cytotoxic T Cells ◽  
Fetal Loss ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Th1 Cytokine ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Th1 Cytokines

ABSTRACT The fetal allograft poses an immunological challenge: how is it protected while immunity to pathogens, particularly those that replicate in the placenta, is maintained? Several theories have been proposed to explain this fetal protection, including a pregnancy-based bias towards a Th2 rather than Th1 cytokine profile in order to avoid generating cytotoxic T cells that could threaten the fetus. Listeria monocytogenes preferentially replicates in the placenta and systemically requires a Th1 response for sterile eradication. In the placenta, the Th1 cytokines tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) are also synthesized in response to this pathogen, without fetal loss. Here we show, by using mice homozygous for null mutations in either the cytokine or cytokine receptor genes, a requirement for both TNF-α and IFN-γ signaling for an effective placental immune response to L. monocytogenes. However, T cells were not recruited to the placenta. Genetic studies in which the fetal component of the placenta was genetically different from the mother indicated that both the production of and response to these cytokines were maternal. Despite the requirement for these cytokines, the early recruitment of neutrophils to the placenta was normal. Consequently, the bacterium appeared to be delayed in its colonization of this organ and did not fully gain hold until 72 h postinfection. These data show a requirement for Th1 cytokines during pregnancy for effective immunity and indicate that a bias away from Th1 cytokine synthesis is not a necessary prerequisite of pregnancy.

scholarly journals Chlamydia muridarum T-Cell Antigens Formulated with the Adjuvant DDA/TDB Induce Immunity against Infection That Correlates with a High Frequency of Gamma Interferon (IFN-γ)/Tumor Necrosis Factor Alpha and IFN-γ/Interleukin-17 Double-Positive CD4+ T Cells

2010 ◽  
Vol 78 (5) ◽  
pp. 2272-2282 ◽  
Author(s):  
Hong Yu ◽  
Xiaozhou Jiang ◽  
Caixia Shen ◽  
Karuna P. Karunakaran ◽  
Janina Jiang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interleukin 17 ◽  
Double Positive ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
T Cell Antigens ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Major impediments to developing a Chlamydia vaccine lie in identifying immunologically relevant T-cell antigens and delivery in a manner to stimulate protective immunity. Using an immunoproteomic approach, we previously identified three immunodominant Chlamydia T-cell antigens (PmpG-1, PmpE/F-2, and RplF). Because RplF has high homology to a human ortholog, it may not be suitable for human vaccine development. Therefore, in this study, we evaluated protection against Chlamydia infection in the genital tract in C57BL/6 mice immunized with Chlamydia-specific membrane proteins PmpG-1, PmpE/F-2, and major outer membrane protein (MOMP; as a reference) or a combination of them formulated with one of three adjuvants, CpG oligodeoxynucleotide (CpG-ODN), AbISCO-100 (AbISCO), or DDA/TDB (dimethyldioctadecylammonium bromide/d-(+)-trehalose 6,6′-dibehenate). The results show that immunization with the CpG-ODN formulation failed to provide protection against Chlamydia infection; the AbISCO formulation conferred moderate protection, and the DDA/TDB formulation showed the highest degree of protective efficacy. The combination of PmpG-1, PmpE/F-2, and MOMP proteins formulated with DDA/TDB exhibited the greatest degree of protection among all vaccine groups studied. Moreover, this vaccine combination also engendered significant protection in BALB/c mice, which have a different major histocompatibility complex (MHC) background. We measured cell-mediated immune cytokine responses in mice immunized with PmpG-1 mixed with each of the three adjuvants. The results demonstrate that mice immunized with the DDA/TDB formulation induced the strongest gamma interferon (IFN-γ) and interleukin-17 (IL-17) responses, characterized by the highest frequency of IFN-γ/tumor necrosis factor alpha (TNF-α) and IFN-γ/IL-17 double-positive CD4+ T cells. In conclusion, a Chlamydia vaccine based on the recombinant proteins PmpG-1, PmpE/F-2, and MOMP delivered in a DDA/TDB adjuvant conferred protection against infection that correlated with IFN-γ/TNF-α and IFN-γ/IL-17 double-positive CD4+ T cells.

scholarly journals T Cells Are Essential for Bacterial Clearance, and Gamma Interferon, Tumor Necrosis Factor Alpha, and B Cells Are Crucial for Disease Development in Coxiella burnetii Infection in Mice

2007 ◽  
Vol 75 (7) ◽  
pp. 3245-3255 ◽  
Author(s):  
Masako Andoh ◽  
Guoquan Zhang ◽  
Kasi E. Russell-Lodrigue ◽  
Heather R. Shive ◽  
Brad R. Weeks ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Q Fever ◽  
Bacterial Clearance ◽  
Histopathological Changes ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Coxiella burnetii, the etiological agent of Q fever, has two phase variants. Phase I has a complete lipopolysaccharide (LPS), is highly virulent, and causes Q fever in humans and pathology in experimental animals. Phase II lacks an LPS O side chain, is avirulent, and does not grow well in immunocompetent animals. To understand the pathogenicity of Q fever, we investigated the roles of immune components in animals infected with Nine Mile phase I (NM I) or Nine Mile phase II (NM II) bacteria. Immunodeficient mice, including SCID mice (deficient in T and B cells), SCIDbg mice (deficient in T, B, and NK cells), nude mice (deficient in T cells), muMT mice (deficient in B cells), bg mice (deficient in NK cells), mice deficient in tumor necrosis factor alpha (TNF-α−/− mice), and mice deficient in gamma interferon (IFN-γ−/− mice), were compared for their responses to infection. SCID, SCIDbg, nude, and IFN-γ−/− mice showed high susceptibility to NM I, and TNF-α−/− mice showed modest susceptibility. Disease caused by NM I in SCID, SCIDbg, and nude mice progressed slowly, while disease in IFN-γ−/− and TNF-α−/− mice advanced rapidly. B- and NK-cell deficiencies did not enhance clinical disease development or alter bacterial clearance but did increase the severity of histopathological changes, particularly in the absence of B cells. Mice infected with NM II showed no apparent clinical disease, but T-cell-deficient mice had histopathological changes. These results suggest that T cells are critical for clearance of C. burnetii, either NM I or NM II, that IFN-γ and TNF-α are essential for the early control of infection, and that B cells are important for the prevention of tissue damage.

scholarly journals Serum Cytokine Responses in Primary Pneumonic Plague Patients

2010 ◽  
Vol 18 (1) ◽  
pp. 184-186 ◽  
Author(s):  
Xiaoyi Wang ◽  
Zuyun Wang ◽  
Zhaobiao Guo ◽  
Baiqing Wei ◽  
Fuzhang Tian ◽  
...  
Keyword(s):  
Time Course ◽  
Interleukin 2 ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Necrosis Factor Alpha ◽  
Pneumonic Plague ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACTThe serum levels of interleukin-2 (IL-2), gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-4, IL-6, and IL-10 of pneumonic plague patients were determined by enzyme-linked immunosorbent assay. IL-6 was the only elevated cytokine in the patients, and its level increased with a clear time course, indicating that IL-6 might be a prognostic marker for predicting the progression of plague.

scholarly journals The Predominant CD4+ Th1 Cytokine Elicited to Chlamydia trachomatis Infection in Women Is Tumor Necrosis Factor Alpha and Not Interferon Gamma

2017 ◽  
Vol 24 (4) ◽  
Author(s):  
Stephen J. Jordan ◽  
Kanupriya Gupta ◽  
Brian M. O. Ogendi ◽  
Rakesh K. Bakshi ◽  
Richa Kapil ◽  
...  
Keyword(s):  
T Cells ◽  
Chlamydia Trachomatis ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Th1 Cytokine ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Chlamydia trachomatis infection is the most prevalent bacterial sexually transmitted infection and can cause significant reproductive morbidity in women. There is insufficient knowledge of C. trachomatis-specific immune responses in humans, which could be important in guiding vaccine development efforts. In contrast, murine models have clearly demonstrated the essential role of T helper type 1 (Th1) cells, especially interferon gamma (IFN-γ)-producing CD4+ T cells, in protective immunity to chlamydia. To determine the frequency and magnitude of Th1 cytokine responses elicited to C. trachomatis infection in humans, we stimulated peripheral blood mononuclear cells from 90 chlamydia-infected women with C. trachomatis elementary bodies, Pgp3, and major outer membrane protein and measured IFN-γ-, tumor necrosis factor alpha (TNF-α)-, and interleukin-2 (IL-2)-producing CD4+ and CD8+ T-cell responses using intracellular cytokine staining. The majority of chlamydia-infected women elicited CD4+ TNF-α responses, with frequency and magnitude varying significantly depending on the C. trachomatis antigen used. CD4+ IFN-γ and IL-2 responses occurred infrequently, as did production of any of the three cytokines by CD8+ T cells. About one-third of TNF-α-producing CD4+ T cells coproduced IFN-γ or IL-2. In summary, the predominant Th1 cytokine response elicited to C. trachomatis infection in women was a CD4+ TNF-α response, not CD4+ IFN-γ, and a subset of the CD4+ TNF-α-positive cells produced a second Th1 cytokine.

scholarly journals Spontaneous Cytokine Production and Its Effect on Induced Production

2002 ◽  
Vol 9 (5) ◽  
pp. 1049-1056 ◽  
Author(s):  
Derrick Walker ◽  
Janine Jason ◽  
Kelly Wallace ◽  
Justin Slaughter ◽  
Virginia Whatley ◽  
...  
Keyword(s):  
T Cells ◽  
Cytokine Production ◽  
Ex Vivo ◽  
Interleukin 2 ◽  
Healthy Adults ◽  
Multiparameter Flow Cytometry ◽  
Parasitic Infections ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Cytokines regulate cellular immune activity and are produced by a variety of cells, especially lymphocytes, monocytes, and macrophages. Multiparameter flow cytometry is often used to examine cell-specific cytokine production after in vitro phorbol 12-myristate 13-acetate and ionomycin induction, with brefeldin A or other agents added to inhibit protein secretion. Spontaneous ex vivo production reportedly rarely occurs. We examined the spontaneous production of interleukin 2 (IL-2), IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) by peripheral-blood B lymphocytes, T cells, CD8− T cells, CD8+ T cells, CD3− CD16/56+ lymphocytes (natural killer [NK] cells), CD3+ CD16/56+ lymphocytes (natural T [NT] cells), and/or monocytes of 316 acutely ill hospitalized persons and 62 healthy adults in Malawi, Africa. We also evaluated the relationship between spontaneous and induced cytokine production. In patients, spontaneous TNF-α production occurred most frequently, followed in descending order by IFN-γ, IL-8, IL-4, IL-10, IL-6, and IL-2. Various cells of 60 patients spontaneously produced TNF-α; for 12 of these patients, TNF-α was the only cytokine produced spontaneously. Spontaneous cytokine production was most frequent in the immunoregulatory cells, NK and NT. For IL-2, IL-4, IL-6, IL-8, and IL-10, spontaneous cytokine production was associated with greater induced production. For TNF-α and IFN-γ, the relationships varied by cell type. For healthy adults, IL-6 was the cytokine most often produced spontaneously. Spontaneous cytokine production was not unusual in these acutely ill and healthy persons living in an area where human immunodeficiency virus, mycobacterial, malaria, and assorted parasitic infections are endemic. In such populations, spontaneous, as well as induced, cell-specific cytokine production should be measured and evaluated in relation to various disease states.

scholarly journals Human Immunodeficiency Virus Infection Alters Tumor Necrosis Factor Alpha Production via Toll-Like Receptor-Dependent Pathways in Alveolar Macrophages and U1 Cells

2008 ◽  
Vol 82 (16) ◽  
pp. 7790-7798 ◽  
Author(s):  
Marlynne Q. Nicol ◽  
Jean-Marie Mathys ◽  
Albertina Pereira ◽  
Kevin Ollington ◽  
Michael H. Ieong ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Innate Immune ◽  
Hiv Positive ◽  
Toll Like Receptor ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Immunodeficiency Virus ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Human immunodeficiency virus (HIV)-positive persons are predisposed to pulmonary infections, even after receiving effective highly active antiretroviral therapy. The reasons for this are unclear but may involve changes in innate immune function. HIV type 1 infection of macrophages impairs effector functions, including cytokine production. We observed decreased constitutive tumor necrosis factor alpha (TNF-α) concentrations and increased soluble tumor necrosis factor receptor type II (sTNFRII) in bronchoalveolar lavage fluid samples from HIV-positive subjects compared to healthy controls. Moreover, net proinflammatory TNF-α activity, as measured by the TNF-α/sTNFRII ratio, decreased as HIV-related disease progressed, as manifested by decreasing CD4 cell count and increasing HIV RNA (viral load). Since TNF-α is an important component of the innate immune system and is produced upon activation of Toll-like receptor (TLR) pathways, we hypothesized that the mechanism associated with deficient TNF-α production in the lung involved altered TLR expression or a deficit in the TLR signaling cascade. We found decreased Toll-like receptor 1 (TLR1) and TLR4 surface expression in HIV-infected U1 monocytic cells compared to the uninfected parental U937 cell line and decreased TLR message in alveolar macrophages (AMs) from HIV-positive subjects. In addition, stimulation with TLR1/2 ligand (Pam3Cys) or TLR4 ligand (lipopolysaccharide) resulted in decreased intracellular phosphorylated extracellular signal-regulated kinase and subsequent decreased transcription and expression of TNF-α in U1 cells compared to U937 cells. AMs from HIV-positive subjects also showed decreased TNF-α production in response to these TLR2 and TLR4 ligands. We postulate that HIV infection alters expression of TLRs with subsequent changes in mitogen-activated protein kinase signaling and cytokine production that ultimately leads to deficiencies of innate immune responses that predispose HIV-positive subjects to infection.

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