scholarly journals Platelet Induced Functional Alteration of CD4+ and CD8+ T Cells in HNSCC

2020 ◽  
Vol 21 (20) ◽  
pp. 7507
Author(s):  
Christina Polasky ◽  
Franziska Wendt ◽  
Ralph Pries ◽  
Barbara Wollenberg
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Cell ◽  
Spatial Separation ◽  
Cell Regulation ◽  
Activation Markers ◽  
Indirect Contact ◽  
Cell Functions ◽  
T Cell Regulation ◽  
Regulatory Functions

Platelets (PLT) are the second most abundant cell type in human blood and exert various immune-regulatory functions under both physiological and pathological conditions. In fact, immune cell regulation via platelets has been demonstrated in several studies within the past decade. However, the exact mechanisms behind T cell regulation remain poorly understood. We questioned whether the formation of aggregates of platelets and T cells has an impact on T-cell functions. In the present study, we stimulated PBMC cultures with anti-CD3 and anti-CD28 mABs and cultured them at a PLT: PBMC ratio of 1:1 or 100:1. After 24, 48, and 72 h, PD-1, PD-L1 expression, and proliferation were analyzed on T cells using flow cytometry. Cytokine production was measured in PHA stimulated CD4 cells after 6 h. We found a significant platelet-mediated decrease in PD-1 and PD-L1 expression, proliferation, as well as IFN-γ and TNF-α production. Perturbations also at least partially remained after spatial separation of PLTs from PBMCs in Transwell-assays. T cell-platelet aggregates showed similar levels of activation markers, proliferation, and secreted cytokines as their non-complexed counterparts. Results indicate a platelet mediated regulation of T cells via direct and indirect contact, but only mediocre effects of the complex formation itself.

scholarly journals Mononuclear phagocytes drive Mertk-dependent T cell regulation at autoimmune and tumor sites

2019 ◽  
Author(s):  
Robin S. Lindsay ◽  
Kristen E. Dew ◽  
Erika Rodriguez ◽  
Jennifer C. Whitesell ◽  
Dayna Tracy ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Phagocytes ◽  
Diabetic Patients ◽  
Cell Regulation ◽  
Peripheral Tissues ◽  
Disease Site ◽  
T Cell Regulation ◽  
Cell Arrest

AbstractUnderstanding mechanisms of immune regulation is key to developing effective immunotherapies for autoimmunity and cancer; however, many regulatory mechanisms have not been elucidated. By analyzing T cell motility and activation at the disease site as well as disease progression, we examined the role of mononuclear phagocytes in driving regulation of effector T cells in type 1 diabetes and melanoma. We report that mononuclear phagocytes in the islets impair T cell responsiveness to antigen by preventing antigen-mediated T cell arrest. Mononuclear phagocytes in the autoimmune lesion express the TAM family receptor tyrosine kinase Mertk which functions in efferocytosis. Inhibition or deficiency of Mertk led to a release from T cell regulation characterized by enhanced T cell arrest in pre-diabetic islets and at the tumor site. This T cell arrest was accompanied by increased T cell-antigen presenting cell interactions as well as increased antigen experience and effector function by T cells in the islets. Notably, the effect of Mertk inhibition on T cell regulation was only seen at the disease site in the islets, not in draining lymph nodes. Inhibition of Mertk-dependent T cell regulation culminated in the rapid acceleration of autoimmune pathology and disease. In human islets, the number of Mertk-expressing cells were increased in remaining insulin-containing islets from type 1 diabetic patients, suggesting that they might have a protective role in human disease. These data indicate that Mertk signaling in mononuclear phagocytes drives T cell regulation that functions specifically at the disease site in peripheral tissues through a mechanism that prevents T cell arrest and response to antigen.

Expression of activation markers by human lung T cells after adherence to lung epithelial cells

1994 ◽  
Vol 267 (5) ◽  
pp. L543-L550 ◽  
Author(s):  
B. Bruinier ◽  
F. H. Krouwels ◽  
B. E. Hol ◽  
H. M. Jansen ◽  
T. A. Out ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Airway Epithelial ◽  
Activation Markers ◽  
Ifn Gamma ◽  
Recombinant Interferon ◽  
Cell Functions

Both increased T cell numbers and their increased activation state have implicated an important role for T cells in chronic inflammatory reactions seen in the airways of (allergic) asthmatics. Airway epithelial cells are frequently exposed to stimuli that cause the release of mediators and the expression of cell adhesion molecules. We have examined whether human airway epithelial cells can activate lung-derived T cells. Clonal lung T cells showed an increased adherence to transformed airway epithelial cells that had been exposed previously for 2 h to human recombinant interferon-gamma (IFN-gamma; 100 U/ml). After an additional 16–24 h of culturing in the absence or presence of epithelial cells, T cells expressed increased levels of both the alpha-chain of the interleukin-2 receptor (IL-2R, CD25) and the transferrin receptor (CD71), both markers of T cell activation. T cells apparently activated by epithelial cells, however, did not produce IFN-gamma or IL-4 nor showed an increased proliferation on the addition of IL-2 (5–50 U/ml). The induced adherence to and the activation of T cells by epithelial cells is mediated largely by CD2 and its ligand lymphocyte functional antigen-3, a pathway known to up- and downregulate T cell functions.

CD4 T-Cell Regulation of Cytotoxic T Cells During the Induction Phase of Liver-Induced Spontaneous Tolerance in Rats

Surgery Today ◽  
2005 ◽  
Vol 35 (6) ◽  
pp. 473-479 ◽  
Author(s):  
Tatsuhiro Ishii ◽  
Junzo Yamaguchi ◽  
Weili Gu ◽  
Toshiaki Hashimoto ◽  
Takao Yamamoto ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Cd4 T Cell ◽  
Induction Phase ◽  
Cell Regulation ◽  
T Cell Regulation

Untired Regulatory T Cells: Untying Fatigue from T Cell Regulation in Multiple Sclerosis

2009 ◽  
Vol 62 (6) ◽  
pp. 327-329
Author(s):  
Harald H. Hofstetter ◽  
Vsevolod Smolianov ◽  
Hans-Peter Hartung
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cell Regulation ◽  
T Cell Regulation

scholarly journals Differential IL-2 expression defines developmental fates of follicular versus nonfollicular helper T cells

Science ◽  
2018 ◽  
Vol 361 (6407) ◽  
pp. eaao2933 ◽  
Author(s):  
Daniel DiToro ◽  
Colleen J. Winstead ◽  
Duy Pham ◽  
Steven Witte ◽  
Rakieb Andargachew ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Fate ◽  
Immune Cell ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Immune Functions ◽  
Fate Determination ◽  
Cell Functions ◽  
Tcr Signals

In response to infection, naïve CD4+ T cells differentiate into two subpopulations: T follicular helper (TFH) cells, which support B cell antibody production, and non-TFH cells, which enhance innate immune cell functions. Interleukin-2 (IL-2), the major cytokine produced by naïve T cells, plays an important role in the developmental divergence of these populations. However, the relationship between IL-2 production and fate determination remains unclear. Using reporter mice, we found that differential production of IL-2 by naïve CD4+ T cells defined precursors fated for different immune functions. IL-2 producers, which were fated to become TFH cells, delivered IL-2 to nonproducers destined to become non-TFH cells. Because IL-2 production was limited to cells receiving the strongest T cell receptor (TCR) signals, a direct link between TCR-signal strength, IL-2 production, and T cell fate determination has been established.

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