scholarly journals c-Jun NH2-Terminal Kinase 2 Inhibits Gamma Interferon Production during Anaplasma phagocytophilum Infection

2007 ◽  
Vol 76 (1) ◽  
pp. 308-316 ◽  
Author(s):  
Joao H. F. Pedra ◽  
Jochen Mattner ◽  
Jian Tao ◽  
Steven M. Kerfoot ◽  
Roger J. Davis ◽  
...  
Keyword(s):  
T Cells ◽  
Strong Evidence ◽  
Anaplasma Phagocytophilum ◽  
Critical Role ◽  
Regulatory Protein ◽  
Inhibitory Effect ◽  
Gamma Interferon ◽  
Interferon Production ◽  
Nk T Cells ◽  
Ifn Γ

ABSTRACT Gamma interferon (IFN-γ) plays a critical role in the early eradication of Anaplasma phagocytophilum. However, the mechanisms that regulate IFN-γ production upon infection remain poorly understood. Here we show that c-Jun NH2-terminal kinase 2 (JNK2) inhibits IFN-γ production during A. phagocytophilum infection. jnk2-null mice were more refractory to infection with A. phagocytophilum and produced increased levels of IFN-γ after challenge with the pathogen. The resistance of jnk2-null mice to A. phagocytophilum infection was due to elevated levels of IFN-γ secreted by conventional and natural killer (NK) T cells. The administration of α-galactosylceramide, a strong NK T-cell agonist, increased IFN-γ release and protected mice from A. phagocytophilum, further demonstrating the inhibitory effect of JNK2 on IFN-γ production. Collectively, these findings provide strong evidence that JNK2 is an important regulatory protein for IFN-γ secretion upon challenge with A. phagocytophilum.

scholarly journals Effector CD8+ T Lymphocytes against Liver Stages of Plasmodium yoelii Do Not Require Gamma Interferon for Antiparasite Activity

2008 ◽  
Vol 76 (8) ◽  
pp. 3628-3631 ◽  
Author(s):  
Sumana Chakravarty ◽  
G. Christian Baldeviano ◽  
Michael G. Overstreet ◽  
Fidel Zavala
Keyword(s):  
T Cells ◽  
T Cell ◽  
Protective Immunity ◽  
Critical Role ◽  
Plasmodium Yoelii ◽  
Gamma Interferon ◽  
Parasite Development ◽  
Wild Type ◽  
Ifn Γ

ABSTRACT The protective immune response against liver stages of the malaria parasite critically requires CD8+ T cells. Although the nature of the effector mechanism utilized by these cells to repress parasite development remains unclear, a critical role for gamma interferon (IFN-γ) has been widely assumed based on circumstantial evidence. However, the requirement for CD8+ T-cell-mediated IFN-γ production in protective immunity to this pathogen has not been directly tested. In this report, we use an adoptive transfer strategy with circumsporozoite (CS) protein-specific transgenic T cells to examine the role of CD8+ T-cell-derived IFN-γ production in Plasmodium yoelii-infected mice. We show that despite a marginal reduction in the expansion of naive IFN-γ-deficient CS-specific transgenic T cells, their antiparasite activity remains intact. Further, adoptively transferred IFN-γ-deficient CD8+ T cells were as efficient as their wild-type counterparts in limiting parasite growth in naive mice. Taken together, these studies demonstrate that IFN-γ secretion by CS-specific CD8+ T cells is not essential to protect mice against live sporozoite challenge.

scholarly journals Contribution of CD8+ T Cells to Gamma Interferon Production in Human Tuberculosis

2001 ◽  
Vol 69 (5) ◽  
pp. 3497-3501 ◽  
Author(s):  
Homayoun Shams ◽  
Benjamin Wizel ◽  
Stephen E. Weis ◽  
Buka Samten ◽  
Peter F. Barnes
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Gamma Interferon ◽  
Interferon Production ◽  
Peripheral Blood Mononuclear ◽  
Tuberculosis Patients ◽  
Ifn Γ ◽  
Stimulation Of

ABSTRACT The proportions of peripheral blood mononuclear cells (PBMC), CD4+ T cells, and CD8+ T cells that produce gamma interferon (IFN-γ) in response to Mycobacterium tuberculosis were markedly reduced in tuberculosis patients, particularly in those with severe disease. Depletion of CD4+ but not CD8+ cells prior to stimulation of PBMC with M. tuberculosis abolished IFN-γ production. These results show that (i) IFN-γ production by CD8+ and CD4+ cells correlates with the clinical manifestations ofM. tuberculosis infection and (ii) IFN-γ production by CD8+ cells depends on CD4+ cells.

scholarly journals CD4+ T Cells and Gamma Interferon in the Long-Term Control of Persistent Friend Retrovirus Infection

2001 ◽  
Vol 75 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Michihiro Iwashiro ◽  
Karin Peterson ◽  
Ronald J. Messer ◽  
Ingunn M. Stromnes ◽  
Kim J. Hasenkrug
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiviral Activity ◽  
Inhibitory Effect ◽  
Gamma Interferon ◽  
Friend Virus ◽  
Virus Infections ◽  
T Cell Clone ◽  
Ifn Γ

ABSTRACT We have used the Friend virus model to determine the basic mechanisms by which the immune system can control persistent retroviral infections. Previously we showed that CD4+ T cells play an essential role in keeping persistent retrovirus in check. The present in vitro experiments with a Friend virus-specific CD4+T-cell clone revealed that these cells produce gamma interferon (IFN-γ), which acts with two distinct mechanisms of antiviral activity. First, IFN-γ had a direct inhibitory effect on virus production. This inhibitory effect was noncytolytic and, interestingly, was not associated with decreased cell surface expression of viral antigens. The second mechanism of IFN-γ-mediated antiviral activity was an enhancement of CD4+ T-cell-mediated cytolytic activity. We also found an in vivo role for IFN-γ in the control of persistent Friend virus infections. Neutralization of IFN-γ in persistently infected mice resulted in significantly increased levels of virus in the spleen, and a significant percentage of IFN-γ-deficient mice were unable to maintain long-term control over Friend virus infections.

scholarly journals Contribution of NK, NK T, γδ T, and αβ T Cells to the Gamma Interferon Response Required for Liver Protection against Trypanosoma cruzi

2006 ◽  
Vol 74 (4) ◽  
pp. 2031-2042 ◽  
Author(s):  
Luiz Roberto Sardinha ◽  
Rosa Maria Elias ◽  
Tainá Mosca ◽  
Karina R. B. Bastos ◽  
Cláudio R. F. Marinho ◽  
...  
Keyword(s):  
T Cells ◽  
Trypanosoma Cruzi ◽  
Nk Cells ◽  
Γδ T Cells ◽  
Gamma Interferon ◽  
Cell Populations ◽  
Liver Protection ◽  
Nk T Cells ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACT In the present work, we show that intracellular Trypanosoma cruzi is rarely found in the livers of acutely infected mice, but inflammation is commonly observed. The presence of numerous intrahepatic amastigotes in infected gamma interferon (IFN-γ)-deficient mice corroborates the notion that the liver is protected by an efficient local immunity. The contribution of different cell populations was suggested by data showing that CD4- and CD8-deficient mice were able to restrain liver parasite growth. Therefore, we have characterized the liver-infiltrating lymphocytes and determined the sources of IFN-γ during acute T. cruzi infection. We observed that natural killer (NK) cells increased by day 7, while T and B cells increased by day 14. Among CD3+ cells, CD4+, CD8+, and CD4− CD8− cell populations were greatly expanded. A large fraction of CD3+ cells were positive for PanNK, a β1 integrin expressed by NK and NK T cells. However, these lymphocytes were not classic NK T cells because they did not express NK1.1 and showed no preferential usage of Vβ8. Otherwise, liver NK T (CD3+ NK1.1+) cells were not increased in acutely infected mice. The majority of PanNK+ CD4+ and PanNK+ CD8+ cells expressed T-cell receptor αβ (TCRαβ), whereas PanNK+ CD4− CD8− cells were positive for TCRγδ. In fact, γδ T cells showed the most remarkable increase (40- to 100-fold) among liver lymphocytes. Most importantly, intracellular analysis revealed high levels of IFN-γ production at day 7 by NK cells and at day 14 by CD4+, CD8+, and CD4− CD8− TCRγδ+ cells. We concluded that NK cells are a precocious source of IFN-γ in the livers of acutely infected mice, and, as the disease progresses, conventional CD4+ and CD8+ T cells and γδ T cells, but not classic NK-T cells, may provide the IFN-γ required for liver protection against T. cruzi.

scholarly journals Antigen-Specific CD4+T Cell-Derived Gamma Interferon Is Both Necessary and Sufficient for ClearingChlamydiafrom the Small Intestine but Not the Large Intestine

2019 ◽  
Vol 87 (6) ◽  
Author(s):  
Hui Lin ◽  
Conghui He ◽  
John J. Koprivsek ◽  
Jianlin Chen ◽  
Zhiguang Zhou ◽  
...  
Keyword(s):  
T Cells ◽  
Small Intestine ◽  
Gastrointestinal Tract ◽  
T Cell ◽  
Large Intestine ◽  
Genital Tract ◽  
Critical Role ◽  
Gamma Interferon ◽  
Content Type ◽  
Ifn Γ

ABSTRACTThe genital tract pathogenChlamydia trachomatisis frequently detected in the gastrointestinal tract, but the host immunity that regulates chlamydial colonization in the gut remains unclear. In aChlamydia muridarum-C57 mouse model, chlamydial organisms are cleared from the genital tract in ∼4 weeks, but the genital organisms can spread to the gastrointestinal tract. We found that the gastrointestinal chlamydial organisms were cleared from the small intestine by day 28, paralleling their infection course in the genital tract, but persisted in the large intestine for long periods. Mice deficient in α/β T cells or CD4+T cells but not CD8+T cells showed chlamydial persistence in the small intestine, indicating a critical role for CD4+T cells in clearingChlamydiafrom the small intestine. The CD4+T cell-dependent clearance is likely mediated by gamma interferon (IFN-γ), since mice deficient in IFN-γ but not interleukin 22 (IL-22) signaling pathways rescued chlamydial colonization in the small intestine. Furthermore, exogenous IFN-γ was sufficient for clearingChlamydiafrom the small intestine but not the large intestine. Mice deficient in developingChlamydia-specific Th1 immunity showed chlamydial persistence in the small intestine. Finally, IFN-γ-producing CD4+but not CD8+T cells from immunized donor mice were sufficient for eliminatingChlamydiafrom the small intestine but not the large intestine of recipient mice. Thus, we have demonstrated a critical role for Th1 immunity in clearingChlamydiafrom the small intestine but not the large intestine, indicating that chlamydial colonization in different regions of the gastrointestinal tract is regulated by distinct immune mechanisms.

scholarly journals Interleukin-4 Receptor α Chain and STAT6 Signaling Inhibit Gamma Interferon but Not Th2 Cytokine Expression within Schistosome Granulomas

2002 ◽  
Vol 70 (10) ◽  
pp. 5651-5658 ◽  
Author(s):  
Ahmed Metwali ◽  
Arthur Blum ◽  
David E. Elliott ◽  
Joel V. Weinstock
Keyword(s):  
T Cells ◽  
Flow Analysis ◽  
Cell Development ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
Th2 Cytokine ◽  
Th2 Cell ◽  
Nk T Cells ◽  
Ifn Γ ◽  
Interleukin 4 Receptor

ABSTRACT Compared to wild-type (WT) mice, schistosome granulomas in Stat6 knockout (KO) mice lacked eosinophils and had Th1 features. Interleukin-4 (IL-4) acts through Stat6 in assisting Th2 cell development. The importance of Stat6 for Th2-cell development within schistosome granulomas had not been explored. Therefore we studied gamma interferon (IFN-γ), IL-4, and IL-5 production in granulomas from Stat6 KO and WT mice. Dispersed granuloma cells from Stat6 KO and WT mice made similar amounts of IL-4 and IL-5. Only Stat6 KO granuloma cells released IFN-γ. Granuloma T cells contained most of the IL-4, IL-5, and IFN-γ mRNA and secreted these cytokines. In Stat6 KO mice, 16.6% of the granuloma cells were CD4+. Of these, 10.7% stained for IFN-γ and/or IL-4 by intracytoplasmic flow analysis. Few CD4− T cells stained positively. The IL-4-producing T cells did not stain for DX5 or with labeled α-GalCer CD1d tetramer, suggesting an absence of NK T cells. Thus, conventional Th cells in Stat6 KO granulomas produce IFN-γ and Th2 cytokines. Stat6 limits IFN-γ production but is unnecessary for Th2-cell development or localization within the granuloma.

scholarly journals Populations of Human T Lymphocytes That Traverse the Vascular Endothelium Stimulated by Borrelia burgdorferi Are Enriched with Cells That Secrete Gamma Interferon

2004 ◽  
Vol 72 (3) ◽  
pp. 1530-1536 ◽  
Author(s):  
Edna I. Gergel ◽  
Martha B. Furie
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Vascular Endothelium ◽  
Human Peripheral Blood ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
Ifn Γ

ABSTRACT Some diseases are characterized by prevalence in the affected tissues of type 1 T lymphocytes, which secrete gamma interferon (IFN-γ) and other proinflammatory cytokines. For example, type 1 T cells predominate in the lesions of patients with Lyme disease, which is caused by the bacterium Borrelia burgdorferi. We used an in vitro model of the blood vessel wall to test the premise that the vascular endothelium actively recruits circulating type 1 T cells to such lesions. When T lymphocytes isolated from human peripheral blood were examined, the populations that traversed monolayers of resting human umbilical vein endothelial cells (HUVEC) or HUVEC stimulated by interleukin-1β or B. burgdorferi were markedly enriched for T cells that produced IFN-γ compared to the initially added population of T cells. No enrichment was seen for cells that produced interleukin-4, a marker for type 2 T lymphocytes. Very late antigen-4 and CD11/CD18 integrins mediated passage of the T cells across both resting and stimulated HUVEC, and the endothelium-derived chemokine CCL2 (monocyte chemoattractant protein 1) was responsible for the enhanced migration of T cells across stimulated HUVEC. These results suggest that the vascular endothelium may contribute to the selective accumulation of type 1 T cells in certain pathological lesions, including those of Lyme disease.

scholarly journals Loss of IFN-γ Production by Invariant NK T Cells in Advanced Cancer

2001 ◽  
Vol 167 (7) ◽  
pp. 4046-4050 ◽  
Author(s):  
Syed Muhammad Ali Tahir ◽  
Olivia Cheng ◽  
Angela Shaulov ◽  
Yasuhiko Koezuka ◽  
Glenn J. Bubley ◽  
...  
Keyword(s):  
T Cells ◽  
Advanced Cancer ◽  
Nk T Cells ◽  
Ifn Γ

scholarly journals Modulation of an Interleukin-12 and Gamma Interferon Synergistic Feedback Regulatory Cycle of T-Cell and Monocyte Cocultures by Porphyromonas gingivalis Lipopolysaccharide in the Absence or Presence of Cysteine Proteinases

2002 ◽  
Vol 70 (10) ◽  
pp. 5695-5705 ◽  
Author(s):  
Peter L. W. Yun ◽  
Arthur A. DeCarlo ◽  
Charles Collyer ◽  
Neil Hunter
Keyword(s):  
T Cells ◽  
T Cell ◽  
Porphyromonas Gingivalis ◽  
Gamma Interferon ◽  
Periodontal Pathogen ◽  
Interleukin 12 ◽  
Minor Role ◽  
Cysteine Proteinases ◽  
Activated T Cells ◽  
Ifn Γ

ABSTRACT Interleukin 12 (IL-12) is an efficient inducer and enhancer of gamma interferon (IFN-γ) production by both resting and activated T cells. There is evidence that human monocytes exposed to IFN-γ have enhanced ability to produce IL-12 when stimulated with lipopolysaccharide (LPS). In this study, it was demonstrated that LPS from the oral periodontal pathogen Porphyromonas gingivalis stimulated monocytes primed with IFN-γ to release IL-12, thereby enhancing IFN-γ accumulation in T-cell populations. P. gingivalis LPS was shown to enhance IL-12 induction of IFN-γ in T cells in a manner independent from TNF-α contribution. The levels of T-cell IL-12 receptors were not affected by P. gingivalis LPS and played only a minor role in the magnitude of the IFN-γ response. These data suggest that LPS from P. gingivalis establishes an activation loop with IL-12 and IFN-γ with potential to augment the production of inflammatory cytokines in relation to the immunopathology of periodontitis. We previously reported that the major cysteine proteinases (gingipains) copurifying with LPS in this organism were responsible for reduced IFN-γ accumulation in the presence of IL-12. However, the addition of the gingipains in the presence of LPS resulted in partial restoration of the IFN-γ levels. In the destructive periodontitis lesion, release of gingipains from the outer membrane (OM) of P. gingivalis could lead to the downregulation of Th1 responses, while gingipain associated with LPS in the OM or in OM vesicles released from the organism could have net stimulatory effects.

IL-36R ligands are potent regulators of dendritic and T cells

Blood ◽  
2011 ◽  
Vol 118 (22) ◽  
pp. 5813-5823 ◽  
Author(s):  
Solenne Vigne ◽  
Gaby Palmer ◽  
Céline Lamacchia ◽  
Praxedis Martin ◽  
Dominique Talabot-Ayer ◽  
...  
Keyword(s):  
T Cells ◽  
Mhc Class Ii ◽  
Critical Role ◽  
T Helper ◽  
Innate And Adaptive Immunity ◽  
Murine Bone Marrow ◽  
Intracellular Signals ◽  
Tnf Α ◽  
Ifn Γ

Abstract IL-36α (IL-1F6), IL-36β (IL-1F8), and IL-36γ (IL-1F9) are members of the IL-1 family of cytokines. These cytokines bind to IL-36R (IL-1Rrp2) and IL-1RAcP, activating similar intracellular signals as IL-1, whereas IL-36Ra (IL-1F5) acts as an IL-36R antagonist (IL-36Ra). In this study, we show that both murine bone marrow-derived dendritic cells (BMDCs) and CD4+ T lymphocytes constitutively express IL-36R and respond to IL-36α, IL-36β, and IL-36γ. IL-36 induced the production of proinflammatory cytokines, including IL-12, IL-1β, IL-6, TNF-α, and IL-23 by BMDCs with a more potent stimulatory effect than that of other IL-1 cytokines. In addition, IL-36β enhanced the expression of CD80, CD86, and MHC class II by BMDCs. IL-36 also induced the production of IFN-γ, IL-4, and IL-17 by CD4+ T cells and cultured splenocytes. These stimulatory effects were antagonized by IL-36Ra when used in 100- to 1000-fold molar excess. The immunization of mice with IL-36β significantly and specifically promoted Th1 responses. Our data thus indicate a critical role of IL-36R ligands in the interface between innate and adaptive immunity, leading to the stimulation of T helper responses.

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