scholarly journals Nonredundant Roles for CD1d-restricted Natural Killer T Cells and Conventional CD4+ T Cells in the Induction of Immunoglobulin E Antibodies in Response to Interleukin 18 Treatment of Mice

2003 ◽  
Vol 197 (8) ◽  
pp. 997-1005 ◽  
Author(s):  
Tomohiro Yoshimoto ◽  
Booki Min ◽  
Takaaki Sugimoto ◽  
Nobuki Hayashi ◽  
Yuriko Ishikawa ◽  
...  
Keyword(s):  
T Cells ◽  
Natural Killer ◽  
Cd4 T Cells ◽  
Immunoglobulin E ◽  
Allergic Inflammation ◽  
Cd40 Ligand ◽  
Nkt Cells ◽  
Class Ii ◽  
Natural Killer T

Interleukin (IL)-18 synergizes with IL-12 to promote T helper cell (Th)1 responses. Somewhat paradoxically, IL-18 administration alone strongly induces immunoglobulin (Ig)E production and allergic inflammation, indicating a role for IL-18 in the generation of Th2 responses. The ability of IL-18 to induce IgE is dependent on CD4+ T cells, IL-4, and signal transducer and activator of transcription (stat)6. Here, we show that IL-18 fails to induce IgE both in CD1d−/− mice that lack natural killer T (NKT) cells and in class II−/− mice that lack conventional CD4+ T cells. However, class II−/− mice reconstituted with conventional CD4+ T cells show the capacity to produce IgE in response to IL-18. NKT cells express high levels of IL-18 receptor (R)α chain and produce significant amounts of IL-4, IL-9, and IL-13, and induce CD40 ligand expression in response to IL-2 and IL-18 stimulation in vitro. In contrast, conventional CD4+ T cells express low levels of IL-18Rα and poorly respond to IL-2 and IL-18. Nevertheless, conventional CD4+ T cells are essential for B cell IgE responses after the administration of IL-18. These findings indicate that NKT cells might be the major source of IL-4 in response to IL-18 administration and that conventional CD4+ T cells demonstrate their helper function in the presence of NKT cells.

scholarly journals Mechanisms imposing the Vβ bias of Vα14 natural killer T cells and consequences for microbial glycolipid recognition

2006 ◽  
Vol 203 (5) ◽  
pp. 1197-1207 ◽  
Author(s):  
Datsen G. Wei ◽  
Shane A. Curran ◽  
Paul B. Savage ◽  
Luc Teyton ◽  
Albert Bendelac
Keyword(s):  
T Cells ◽  
Natural Killer ◽  
Optimal Solution ◽  
Nkt Cells ◽  
Cell Repertoire ◽  
Transgenic Cells ◽  
Α Chain ◽  
Natural Killer T

Mouse and human natural killer T (NKT) cells recognize a restricted set of glycosphingolipids presented by CD1d molecules, including self iGb3 and microbial α-glycuronosylceramides. The importance of the canonical Vα14-Jα18 TCR α chain for antigen recognition by NKT cells is well recognized, but the mechanisms underlying the Vβ8, Vβ7, and Vβ2 bias in mouse have not been explored. To study the influences of thymic selection and the constraints of pairing with Vα14-Jα18, we have created a population of mature T cells expressing Vα14-Jα18 TCR α chain in CD1d-deficient mice and studied its recognition properties in vitro and in vivo. Transgenic cells expressed a diverse Vβ repertoire but their recognition of endogenous ligands and synthetic iGb3 was restricted to the same biased Vβ repertoire as expressed in natural NKT cells. In contrast, α-GalCer, a synthetic homologue of microbial α-glycuronosylceramides, was recognized by a broader set of Vβ chains, including the biased NKT set but also Vβ6, Vβ9, Vβ10, and Vβ14. These surprising findings demonstrate that, whereas Vβ8, Vβ7, and Vβ2 represent the optimal solution for recognition of endogenous ligand, many Vβ chains that are potentially useful for the recognition of foreign lipids fail to be selected in the NKT cell repertoire.

Impact of activated invariant natural killer T cells on the expansion of regulatory T cell precursors in murine thymocytes in vitro

2019 ◽  
Vol 206 ◽  
pp. 41-48
Author(s):  
Haruki Katsumata ◽  
Masako Ikemiyagi ◽  
Toshihito Hirai ◽  
Taichi Kanzawa ◽  
Rumi ishii ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
Regulatory T Cell ◽  
Natural Killer T Cells ◽  
Killer T Cells ◽  
Invariant Natural Killer ◽  
Natural Killer T

scholarly journals Type I Natural Killer T Cells as Key Regulators of the Immune Response to Infectious Diseases

2020 ◽  
Vol 34 (2) ◽  
pp. e00232-20
Author(s):  
Nicolás M. S. Gálvez ◽  
Karen Bohmwald ◽  
Gaspar A. Pacheco ◽  
Catalina A. Andrade ◽  
Leandro J. Carreño ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Infectious Diseases ◽  
Natural Killer ◽  
Nkt Cells ◽  
Interleukin 4 ◽  
Type I ◽  
Inkt Cells ◽  
Class I Mhc ◽  
Natural Killer T

SUMMARYThe immune system must work in an orchestrated way to achieve an optimal response upon detection of antigens. The cells comprising the immune response are traditionally divided into two major subsets, innate and adaptive, with particular characteristics for each type. Type I natural killer T (iNKT) cells are defined as innate-like T cells sharing features with both traditional adaptive and innate cells, such as the expression of an invariant T cell receptor (TCR) and several NK receptors. The invariant TCR in iNKT cells interacts with CD1d, a major histocompatibility complex class I (MHC-I)-like molecule. CD1d can bind and present antigens of lipid nature and induce the activation of iNKT cells, leading to the secretion of various cytokines, such as gamma interferon (IFN-γ) and interleukin 4 (IL-4). These cytokines will aid in the activation of other immune cells following stimulation of iNKT cells. Several molecules with the capacity to bind to CD1d have been discovered, including α-galactosylceramide. Likewise, several molecules have been synthesized that are capable of polarizing iNKT cells into different profiles, either pro- or anti-inflammatory. This versatility allows NKT cells to either aid or impair the clearance of pathogens or to even control or increase the symptoms associated with pathogenic infections. Such diverse contributions of NKT cells to infectious diseases are supported by several publications showing either a beneficial or detrimental role of these cells during diseases. In this article, we discuss current data relative to iNKT cells and their features, with an emphasis on their driving role in diseases produced by pathogenic agents in an organ-oriented fashion.

scholarly journals Natural Killer Dendritic Cells Enhance Immune Responses Elicited byα-Galactosylceramide-Stimulated Natural Killer T Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Sung Won Lee ◽  
Hyun Jung Park ◽  
Nayoung Kim ◽  
Seokmann Hong
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Natural Killer ◽  
Immune Cells ◽  
Tumor Antigens ◽  
Nkt Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Natural Killer T

Natural killer dendritic cells (NKDCs) possess potent anti-tumor activity, but the cellular effect of NKDC interactions with other innate immune cells is unclear. In this study, we demonstrate that the interaction of NKDCs and natural killer T (NKT) cells is required for the anti-tumor immune responses that are elicited byα-galactosylceramide (α-GC) in mice. The rapid and strong expression of interferon-γby NKDCs afterα-GC stimulation was dependent on NKT cells. Various NK and DC molecular markers and cytotoxic molecules were up-regulated followingα-GC administration. This up-regulation could improve NKDC presentation of tumor antigens and increase cytotoxicity against tumor cells. NKDCs were required for the stimulation of DCs, NK cells, and NKT cells. The strong anti-tumor immune responses elicited byα-GC may be due to the down-regulation of regulatory T cells. Furthermore, the depletion of NKDCs dampened the tumor clearance mediated byα-GC-stimulated NKT cellsin vivo. Taken together, these results indicate that complex interactions of innate immune cells might be required to achieve optimal anti-tumor immune responses during the early stages of tumorigenesis.

Elevated CD54 Expression Renders CD4+ T Cells Susceptible to Natural Killer Cell-Mediated Killing

2019 ◽  
Vol 220 (12) ◽  
pp. 1892-1903 ◽  
Author(s):  
Xi Chen ◽  
Huihui Chen ◽  
Zining Zhang ◽  
Yajing Fu ◽  
Xiaoxu Han ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Cd4 T Cells ◽  
Nk Cell ◽  
Killer Cell ◽  
Adaptive Immune Response ◽  
Phenotypic Analysis

Abstract Background Natural killer (NK) cells are an important type of effector cell in the innate immune response, and also have a role in regulation of the adaptive immune response. Several studies have indicated that NK cells may influence CD4+ T cells during HIV infection. Methods In total, 51 HIV-infected individuals and 15 healthy controls participated in this study. We performed the flow cytometry assays and real-time PCR for the phenotypic analysis and the functional assays of NK cell-mediated deletion of CD4+ T cells, phosphorylation of nuclear factor-κB (NF-κB/p65) and the intervention of metformin. Results Here we detected high CD54 expression on CD4+ T cells in HIV-infected individuals, and demonstrate that upregulated CD54 is associated with disease progression in individuals infected with HIV. We also show that CD54 expression leads to the deletion of CD4+ T cells by NK cells in vitro, and that this is modulated by NF-κB/p65 signaling. Further, we demonstrate that metformin can suppress CD54 expression on CD4+ T cells by inhibiting NF-κB/p65 phosphorylation. Conclusions Our data suggest that further studies to evaluate the potential role of metformin as adjunctive therapy to reconstitute immune function in HIV-infected individuals are warranted.

scholarly journals Role of CXCR6-Deficient Natural Killer T Cells and CD4 T Cells in Hepatocarcinogenesis

2019 ◽  
Vol 157 (4) ◽  
pp. 1169-1170
Author(s):  
Huan Tao ◽  
Xuyong Chen
Keyword(s):  
T Cells ◽  
Natural Killer ◽  
Cd4 T Cells ◽  
Natural Killer T Cells ◽  
Killer T Cells ◽  
Natural Killer T

scholarly journals Selective effects of radiotherapy on viability and function of invariant natural killer T cells in vitro

2020 ◽  
Vol 145 ◽  
pp. 128-136
Author(s):  
Ashanty M. Melo ◽  
Stephen G. Maher ◽  
Seónadh M. O'Leary ◽  
Derek G. Doherty ◽  
Joanne Lysaght
Keyword(s):  
T Cells ◽  
Natural Killer ◽  
Natural Killer T Cells ◽  
And Function ◽  
Killer T Cells ◽  
Invariant Natural Killer ◽  
Selective Effects ◽  
Natural Killer T

In Vitro Expansion of Autologous Follicular Lymphoma-Specific T Cells for Adoptive Transfer.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1482-1482
Author(s):  
Seung-Tae Lee ◽  
Yun Fang Jiang ◽  
Soung-Chul Cha ◽  
Hong Qin ◽  
Larry W. Kwak ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Follicular Lymphoma ◽  
Tumor Cells ◽  
Cd4 T Cells ◽  
Cd40 Ligand ◽  
Autologous Tumor ◽  
T Cell Lines

Abstract Advanced stage follicular lymphoma remains an incurable disease with a median survival of 8 to 10 years that has not significantly changed over the last four decades. Therefore, novel treatment options are necessary to improve the clinical outcome in these patients. The observation of spontaneous regressions in a small percentage of patients suggested that augmenting the host immune response could potentially control this malignancy. Strategies using active specific immunotherapy with idiotype vaccines led to induction of clinical and molecular responses in a few patients but have met with only limited success possibly due to the low frequency of antigen-specific T cells induced in the patients. In contrast to active immunization, T cells of a given specificity and function may be selected and expanded in vitro to the desired number for adoptive cell transfer. Towards this goal, we stimulated tumor infiltrating lymphocytes (TILs) or peripheral blood mononuclear cells (PBMCs) from five follicular lymphoma patients with CD40 ligand-activated autologous tumor cells at approximately ten-day intervals in the presence of IL-2 and IL-15. After four rounds of stimulations, T cell lines generated from 3/5 patients recognized autologous unmodified tumor cells by producing significant amounts of TNF-α, GM-CSF and/or IFN-γ. By phenotypic analysis, the T cell lines were predominantly CD4+ T cells (> 70%), and intracellular cytokine assay showed that up to 40% of the CD4+ T cells were tumor-reactive. The inhibition of cytokine production by anti-HLA class II but not class I blocking antibodies confirmed that the CD4+ T cells were tumor-reactive. Further characterization revealed that the T cells from one patient recognized autologous tumor but not autologous normal B cells suggesting that they were tumor-specific. While in a second patient CD4+ T cell clones generated from the T cell line by limiting dilution recognized autologous tumor and autologous normal B cells but not autologous monocytes suggesting that they were B cell lineage-specific. We conclude that follicular lymphoma-specific T cells exist and can be efficiently expanded in vitro from both TILs and PBMCs using CD40 ligand-activated autologous tumor cells for adoptive T cell therapy. Additionally, identification of antigens recognized by these T cells could lead to development of novel immunotherapeutic strategies for lymphomas.

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