Faculty Opinions recommendation of Commensal microbiota and CD8+ T cells shape the formation of invariant NKT cells.

Abstract NKT cells from naïve mice are mainly CD4+ or CD4−CD8−. However, it has been reported that CD8+ NKT cells can be expanded in vitro from splenocytes, bone marrow cells and thymocytes of C57BL/6 (B6) mice by stimulation with anti-CD3 mAb and cytokines, and that the expanded CD8+ NKT cells mediate strong graft-vs.-leukemic (GVL) effects without severe GVHD after adoptive transfer into allogeneic mice. We now describe the presence of CD8+NK1.1+ cells in recipient livers (approximately 2–6%), but not in other tissues (spleen, lung, bone marrow, thymus and PBMC), in various allogeneic hematopoietic cell transplantation (allo-HCT) models. The generation of CD8+NK1.1+ cells is likely a consequence of alloresponses, as these cells were not detected in the liver of syngeneic HCT controls. Flow cytometric analysis confirmed that these cells are CD1d-independent, TCRαβ+ T cells with a memory phenotype (CD44+ and CD62L−), and do not express CD49b, Ly-49C/I, Ly-49G2, or Ly-49D. In a sublethally (6 Gy)-irradiated B6-to-B6D2F1 allo-HCT model, NK1.1+ CD8 T cells became detectable by week 2, increased in number until approximately week 8, and gradually declined thereafter but were still detectable in the liver at day 100 after allo-HCT. By using CD45.1 and CD45.2 congeneic donors, we determined that the majority of NK1.1+ CD8 T cells were derived from the donor splenocytes. Furthermore, depletion of CD8+, but not NK1.1+, cells from the donor splenocytes prior to transplantation prevented the generation of NK1.1+ CD8 T cells, indicating that these cells were derived from donor NK1.1−CD8+ splenic T cells. Our data demonstrate that donor CD8 T cells can acquire NK1.1 expression upon activation in allo-HCT recipients, and that these NK1.1+ CD8 T cells maintain a memory phenotype and persist in the recipients with preferential accumulation in the liver. Studies are currently in progress to determine the role of activated donor NK1.1+ CD8 T cells in GVHD and GVL effects.

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MP46-18 CD8 T CELLS INHIBIT THE INTERLEUKIN-15 (IL-15) INDUCED CYTOTOXIC ACTIVITY OF NK AND NKT CELLS TOWARD TUMOUR CELLS IN THE PROSTATE CANCER MICROENVIRONMENT.

The Journal of Urology ◽

10.1016/j.juro.2015.02.1581 ◽

2015 ◽

Vol 193 (4S) ◽

Cited By ~ 1

Author(s):

Oussama Elhage ◽

Christina Sakellariou ◽

Richard A. Smith ◽

Christine Galustian ◽

Prokar Dasgupta

Keyword(s):

Prostate Cancer ◽

T Cells ◽

Cytotoxic Activity ◽

Cd8 T Cells ◽

Nkt Cells ◽

Tumour Cells ◽

Cancer Microenvironment ◽

Interleukin 15

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303 Systemic Control of Plasmacytoid Dendritic Cells By CD8+ T Cells and Commensal Microbiota

Gastroenterology ◽

10.1016/s0016-5085(08)60206-1 ◽

2008 ◽

Vol 134 (4) ◽

pp. A-43

Author(s):

Daisuke Fujiwara ◽

Bo Wei ◽

Laura L. Presley ◽

Sarah N. Brewer ◽

Michael McPherson ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Cd8 T Cells ◽

Plasmacytoid Dendritic Cells ◽

Commensal Microbiota ◽

Systemic Control

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Deciphering the Prognostic Implications of the Components and Signatures in the Immune Microenvironment of Pancreatic Ductal Adenocarcinoma

Frontiers in Immunology ◽

10.3389/fimmu.2021.648917 ◽

2021 ◽

Vol 12 ◽

Author(s):

Rong Tang ◽

Xiaomeng Liu ◽

Chen Liang ◽

Jie Hua ◽

Jin Xu ◽

...

Keyword(s):

T Cells ◽

Tumor Microenvironment ◽

Single Cell ◽

Pancreatic Ductal Adenocarcinoma ◽

Cd8 T Cells ◽

Nkt Cells ◽

Ductal Adenocarcinoma ◽

Hematopoietic Stem ◽

Single Cell Sequencing ◽

Prognostic Implications

Background: The treatment modalities for pancreatic ductal adenocarcinoma (PDAC) are limited and unsatisfactory. Although many novel drugs targeting the tumor microenvironment, such as immune checkpoint inhibitors, have shown promising efficacy for some tumors, few of them significantly prolong the survival of patients with PDAC due to insufficient knowledge on the tumor microenvironment.Methods: A single-cell RNA sequencing (scRNA-seq) dataset and seven PDAC cohorts with complete clinical and bulk sequencing data were collected for bioinformatics analysis. The relative proportions of each cell type were estimated using the gene set variation analysis (GSVA) algorithm based on the signatures identified by scRNA-seq or previous literature.Results: A meta-analysis of 883 PDAC patients showed that neutrophils are associated with worse overall survival (OS) for PDAC, while CD8+ T cells, CD4+ T cells, and B cells are related to prolonged OS for PDAC, with marginal statistical significance. Seventeen cell categories were identified by clustering analysis based on single-cell sequencing. Among them, CD8+ T cells and NKT cells were universally exhausted by expressing exhaustion-associated molecular markers. Interestingly, signatures of CD8+ T cells and NKT cells predicted prolonged OS for PDAC only in the presence of “targets” for pyroptosis and ferroptosis induction. Moreover, a specific state of T cells with overexpression of ribosome-related proteins was associated with a good prognosis. In addition, the hematopoietic stem cell (HSC)-like signature predicted prolonged OS in PDAC. Weighted gene co-expression network analysis identified 5 hub genes whose downregulation may mediate the observed survival benefits of the HSC-like signature. Moreover, trajectory analysis revealed that myeloid cells evolutionarily consisted of 7 states, and antigen-presenting molecules and complement-associated genes were lost along the pseudotime flow. Consensus clustering based on the differentially expressed genes between two states harboring the longest pseudotime span identified two PDAC groups with prognostic differences, and more infiltrated immune cells and activated immune signatures may account for the survival benefits.Conclusion: This study systematically investigated the prognostic implications of the components of the PDAC tumor microenvironment by integrating single-cell sequencing and bulk sequencing, and future studies are expected to develop novel targeted agents for PDAC treatment.

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CD70 Inversely Regulates Regulatory T Cells and Invariant NKT Cells and Modulates Type 1 Diabetes in NOD Mice

The Journal of Immunology ◽

10.4049/jimmunol.2000148 ◽

2020 ◽

Vol 205 (7) ◽

pp. 1763-1777

Author(s):

Cheng Ye ◽

Benjamin E. Low ◽

Michael V. Wiles ◽

Todd M. Brusko ◽

David V. Serreze ◽

...

Keyword(s):

T Cells ◽

Type 1 Diabetes ◽

Regulatory T Cells ◽

Nod Mice ◽

Nkt Cells ◽

Invariant Nkt Cells

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Natural killer T cells in lipoprotein metabolism and atherosclerosis

Thrombosis and Haemostasis ◽

10.1160/th11-05-0336 ◽

2011 ◽

Vol 106 (11) ◽

pp. 814-819 ◽

Cited By ~ 28

Author(s):

Godfrey Getz ◽

Paul VanderLaan ◽

Catherine Reardon

Keyword(s):

T Cells ◽

T Cell ◽

Natural Killer ◽

Cell Receptor ◽

Nkt Cells ◽

Inflammatory Disorder ◽

Chronic Inflammatory Disorder ◽

Invariant Nkt Cells ◽

Adaptive Immune ◽

Natural Killer T

SummaryCells of both the innate and adaptive immune system participate in the development of atherosclerosis, a chronic inflammatory disorder of medium and large arteries. Natural killer T (NKT) cells express surface markers characteristic of natural killer cells and conventional T cells and bridge the innate and adaptive immune systems. The development and activation of NKT cells is dependent upon CD1d, a MHC-class I-type molecule that presents lipids, especially glycolipids to the T cell receptors on NKT cells. There are two classes of NKT cells; invariant NKT cells that express a semi-invariant T cell receptor and variant NKT cells. This review summarises studies in murine models in which the effect of the activation, overexpression or deletion of NKT cells or only invariant NKT cells on atherosclerosis has been examined.

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