scholarly journals Prostaglandin D2 Inhibits the Production of IFN-γ by Invariant NK T Cells: Consequences in the Control of B16 Melanoma

2008 ◽  
Vol 180 (2) ◽  
pp. 783-792 ◽  
Author(s):  
David Torres ◽  
Christophe Paget ◽  
Josette Fontaine ◽  
Thierry Mallevaey ◽  
Toshiyuki Matsuoka ◽  
...  
Keyword(s):  
T Cells ◽  
B16 Melanoma ◽  
Prostaglandin D2 ◽  
Nk T Cells ◽  
Ifn Γ

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 Regulation of tumor growth by leukocyte-specific protein 1 in T cells

2020 ◽  
Vol 8 (2) ◽  
pp. e001180
Author(s):  
Riri Kwon ◽  
Bong-Ki Hong ◽  
Kang-Gu Lee ◽  
Eunbyeol Choi ◽  
Laurent Sabbagh ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adoptive Transfer ◽  
Specific Protein ◽  
B16 Melanoma ◽  
Tumor Mass ◽  
T Cell Infiltration ◽  
Tnf Α ◽  
Ifn Γ ◽  
Melanoma Growth

BackgroundClinical efficacy of T cell-based cancer immunotherapy is limited by the lack of T cell infiltration in the tumor mass, especially in solid tumors. Our group demonstrated previously that leukocyte-specific protein 1 (LSP1), an intracellular signal regulator, negatively regulates T cell infiltration in inflamed tissues.MethodsTo determine the immuno-regulatory effects of LSP1 in T cells on tumor progression, we investigated the growth of B16 melanoma in Lsp1 knockout (KO) mice and T cell-specific Lsp1 transgenic (Tg) mice. The immune cell subpopulation infiltrated into the tumor mass as well as the expression of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in T cells was assessed by flow cytometry and/or immunohistochemistry. Chemotactic migration was assayed with Lsp1 KO and Lsp1 Tg T cells. Adoptive transfer of Lsp1 KO or Lsp1 Tg T cells was performed in B16 melanoma-challenged Rag1 KO mice.ResultsLsp1 KO mice showed decreased growth of B16 melanoma and increased infiltration of T cells in the tumor mass, which were completely reversed in T cell-specific Lsp1 Tg mice. Lsp1 KO CD8+ T cells also exhibited elevated migratory capacity in response to CXCL9 and CXCL10, whereas Lsp1 Tg CD8+ T cells did the opposite. LSP1 expression was increased in tumor-infiltrating T cells and could be induced by T cell receptor activation. Intriguingly, gene expression profiling of Lsp1 KO T cells suggested enhanced cytotoxicity. Indeed, expression of IFN-γ and TNF-α was increased in tumor-infiltrating CD4+ and CD8+ T cells of Lsp1 KO mice, while it was markedly reduced in those of Lsp1 Tg mice. Adoptive transfer of Lsp1 KO T cells to Rag1 KO mice was more effective in suppressing melanoma growth than transfer of Lsp1 Tg T cells. Of note, when treated with antiprogrammed cell death protein 1 (PD-1) antibody, inhibition of melanoma growth was more pronounced in Lsp1 KO mice than in Lsp1-sufficient mice, suggesting that Lsp1 depletion additively increases the antitumor effects of anti-PD-1 antibody.ConclusionsLSP1 in T cells regulates the growth of B16 melanoma in mice, possibly by affecting migration and infiltration of T cells into the tumor and by modulating production of antitumor effector cytokines by CD8+ T cells. These findings provide evidence that LSP1 can be a target to improve the efficacy of T cell-based immunotherapy.

scholarly journals NK T Cells Contribute to Expansion of CD8+ T Cells and Amplification of Antiviral Immune Responses to Respiratory Syncytial Virus

2002 ◽  
Vol 76 (9) ◽  
pp. 4294-4303 ◽  
Author(s):  
Teresa R. Johnson ◽  
Seokmann Hong ◽  
Luc Van Kaer ◽  
Yasuhiko Koezuka ◽  
Barney S. Graham
Keyword(s):  
T Cells ◽  
Respiratory Syncytial Virus ◽  
T Lymphocytes ◽  
Immune Responses ◽  
Natural Killer ◽  
Viral Clearance ◽  
Normal Numbers ◽  
Nk T Cells ◽  
Ifn Γ ◽  
Syncytial Virus

ABSTRACT CD1d-deficient mice have normal numbers of T lymphocytes and natural killer cells but lack Vα14+ natural killer T cells. Respiratory syncytial virus (RSV) immunopathogenesis was evaluated in 129×C57BL/6, C57BL/6, and BALB/c CD1d−/− mice. CD8+ T lymphocytes were reduced in CD1d−/− mice of all strains, as shown by cell surface staining and major histocompatibility complex class I tetramer analysis, and resulted in strain-specific alterations in illness, viral clearance, and gamma interferon (IFN-γ) production. Transient activation of NK T cells in CD1d+/+ mice by α-GalCer resulted in reduced illness and delayed viral clearance. These data suggest that early IFN-γ production and efficient induction of CD8+-T-cell responses during primary RSV infection require CD1d-dependent events. We also tested the ability of α-GalCer as an adjuvant to modulate the type 2 immune responses induced by RSV glycoprotein G or formalin-inactivated RSV immunization. However, immunized CD1-deficient or α-GalCer-treated wild-type mice did not exhibit diminished disease following RSV challenge. Rather, some disease parameters, including cytokine production, eosinophilia, and viral clearance, were increased. These findings indicate that CD1d-dependent NK T cells play a role in expansion of CD8+ T cells and amplification of antiviral responses to RSV.

scholarly journals Constitutive Cytokine mRNAs Mark Natural Killer (NK) and NK T Cells Poised for Rapid Effector Function

2003 ◽  
Vol 198 (7) ◽  
pp. 1069-1076 ◽  
Author(s):  
Daniel B. Stetson ◽  
Markus Mohrs ◽  
R. Lee Reinhardt ◽  
Jody L. Baron ◽  
Zhi-En Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Natural Killer ◽  
Thymic Development ◽  
Evolutionary Selection ◽  
Nk T Cells ◽  
Ifn Γ ◽  
Selection For ◽  
Cytokine Mrnas ◽  
Developmental Maturation

Natural killer (NK) and NK T cells are tissue lymphocytes that secrete cytokines rapidly upon stimulation. Here, we show that these cells maintain distinct patterns of constitutive cytokine mRNAs. Unlike conventional T cells, NK T cells activate interleukin (IL)-4 and interferon (IFN)-γ transcription during thymic development and populate the periphery with both cytokine loci previously modified by histone acetylation. Similarly, NK cells transcribe and modify the IFN-γ gene, but not IL-4, during developmental maturation in the bone marrow. Lineage-specific patterns of cytokine transcripts predate infection and suggest evolutionary selection for invariant but distinct types of effector responses among the earliest responding lymphocytes.

scholarly journals Overexpression of CD1d by Keratinocytes in Psoriasis and CD1d-Dependent IFN-γ Production by NK-T Cells

2000 ◽  
Vol 165 (7) ◽  
pp. 4076-4085 ◽  
Author(s):  
Brian Bonish ◽  
Denis Jullien ◽  
Yves Dutronc ◽  
Barbara Bei Huang ◽  
Robert Modlin ◽  
...  
Keyword(s):  
T Cells ◽  
Nk T Cells ◽  
Ifn Γ

scholarly journals Production of Both IL-27 and IFN-γ after the Treatment with a Ligand for Invariant NK T Cells Is Responsible for the Suppression of Th2 Response and Allergic Inflammation in a Mouse Experimental Asthma Model

2009 ◽  
Vol 183 (1) ◽  
pp. 254-260 ◽  
Author(s):  
Hiroyuki Fujita ◽  
Annabelle Teng ◽  
Risa Nozawa ◽  
Yukiko Takamoto-Matsui ◽  
Haruka Katagiri-Matsumura ◽  
...  
Keyword(s):  
T Cells ◽  
Allergic Inflammation ◽  
Th2 Response ◽  
Asthma Model ◽  
Nk T Cells ◽  
Ifn Γ

scholarly journals Gamma Interferon Production by Hepatic NK T Cells during Escherichia coli Infection Is Resistant to the Inhibitory Effects of Oxidative Stress

2003 ◽  
Vol 71 (5) ◽  
pp. 2468-2477 ◽  
Author(s):  
Guochi Zhang ◽  
Robert Dru Nichols ◽  
Masaru Taniguchi ◽  
Toshinori Nakayama ◽  
Michael J. Parmely
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Escherichia Coli ◽  
T Cells ◽  
Nk Cells ◽  
Inhibitory Effects ◽  
Gram Negative ◽  
E Coli ◽  
Nk T Cells ◽  
Ifn Γ

ABSTRACT The reductive-oxidative status of tissues regulates the expression of many inflammatory genes that are induced during gram-negative bacterial infections. The cytokine gamma interferon (IFN-γ) is a potent stimulus for host inflammatory gene expression, and oxidative stress has been shown to inhibit its production in mice challenged with Escherichia coli bacteria. The objective of the present study was to characterize the cells that produced IFN-γ in a mouse bacterial peritonitis model and determine the effects of oxidative stress on their activation. The liver contained large numbers of IFN-γ-expressing lymphocytes following challenge with viable E. coli bacteria. The surface phenotypes of IFN-γ-expressing hepatic lymphocytes were those of natural killer (NK) cells (NK1.1+ CD3−), conventional T cells (NK1.1− CD3+), and NK T cells (NK1.1+ CD3+). Treating mice with diethyl maleate to deplete tissue thiols significantly impaired IFN-γ production by NK cells, conventional T cells, and CD1d-restricted NK T cells in response to E. coli challenge. However, IFN-γ expression by a subset of NK T cells, which did not bind α-galactosylceramide-CD1d tetramers, was resistant to the inhibitory effects of tissue oxidative stress. Stress-resistant IFN-γ-expressing cells were also predominantly CD8+ and bore γδ T-cell antigen receptors. The residual IFN-γ response by NK T cells may explain previous reports of hepatic gene expression following gram-negative bacterial challenge in thiol-depleted mice. The finding also demonstrates that innate immune cells differ significantly in their responses to altered tissue redox status.

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 IL-4-producing NK T cells are biased towards IFN-γ production by IL-12. Influence of the microenvironment on the functional capacities of NK T cells

1998 ◽  
Vol 28 (5) ◽  
pp. 1507-1515 ◽  
Author(s):  
Maria C. Leite-De-Moraes ◽  
Géraldine Moreau ◽  
Anne Arnould ◽  
François Machavoine ◽  
Corinne Garcia ◽  
...  
Keyword(s):  
T Cells ◽  
Nk T Cells ◽  
Ifn Γ ◽  
Functional Capacities

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.

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