scholarly journals Absence of bcl-2 expression by activated CD45RO+ T lymphocytes in acute infectious mononucleosis supporting their susceptibility to programmed cell death

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 521-527
Author(s):  
Y Tamaru ◽  
T Miyawaki ◽  
K Iwai ◽  
T Tsuji ◽  
R Nibu ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Infectious Mononucleosis ◽  
Cd8 T Cells ◽  
Apoptotic Cell ◽  
Flow Cytometric Analysis ◽  
Inner Mitochondrial Membrane ◽  
Activated T Cells ◽  
Acute Infectious Mononucleosis

bcl-2 proto-oncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death (apoptosis). There is now increasing evidence that regulation of bcl-2 expression is a determinant of life or death in normal lymphocytes. We have recently described that activated (CD45RO+) CD4+ and CD8+ T cells in acute infectious mononucleosis (IM) undergo apoptotic cell death on culturing, indicating an activation-driven cell death of mature T cells. In this work, we examine bcl-2 expression by activated T cells in acute IM using a flow-cytometric analysis with an anti-bcl-2 monoclonal antibody (MoAb). It was consistently observed that most T cells from acute IM patients displayed only much less bcl-2, while normal T cells expressed bcl-2 relatively strongly. Multicolor analysis showed that bcl-2- lacking T cells in acute IM were restricted to the CD45RO+ (activated) populations of CD4+, as well as CD8+ T cells. In contrast, the relatively intense levels of bcl-2 were expressed in both CD45RO+ and CD45RO- T-cell populations from normal subjects. This marked difference in bcl-2 expression of CD45RO+ T cells between acute IM and normal controls was also confirmed by Western blot analysis. Activated (CD45RO+) T cells with low bcl-2 expression, but not bcl-2-expressing CD45RO- T cells, in acute IM patients were found to die easily when cultured without added growth factors. However, in normal individuals, both CD45RO+ and CD45RO- T cells were relatively stable on culturing. These findings suggest that lack of bcl-2 expression by activated (CD45RO+) T cells in acute IM might be associated with their susceptibility to programmed cell death.

scholarly journals Absence of bcl-2 expression by activated CD45RO+ T lymphocytes in acute infectious mononucleosis supporting their susceptibility to programmed cell death

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 521-527 ◽  
Author(s):  
Y Tamaru ◽  
T Miyawaki ◽  
K Iwai ◽  
T Tsuji ◽  
R Nibu ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Infectious Mononucleosis ◽  
Cd8 T Cells ◽  
Apoptotic Cell ◽  
Flow Cytometric Analysis ◽  
Inner Mitochondrial Membrane ◽  
Activated T Cells ◽  
Acute Infectious Mononucleosis

Abstract bcl-2 proto-oncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death (apoptosis). There is now increasing evidence that regulation of bcl-2 expression is a determinant of life or death in normal lymphocytes. We have recently described that activated (CD45RO+) CD4+ and CD8+ T cells in acute infectious mononucleosis (IM) undergo apoptotic cell death on culturing, indicating an activation-driven cell death of mature T cells. In this work, we examine bcl-2 expression by activated T cells in acute IM using a flow-cytometric analysis with an anti-bcl-2 monoclonal antibody (MoAb). It was consistently observed that most T cells from acute IM patients displayed only much less bcl-2, while normal T cells expressed bcl-2 relatively strongly. Multicolor analysis showed that bcl-2- lacking T cells in acute IM were restricted to the CD45RO+ (activated) populations of CD4+, as well as CD8+ T cells. In contrast, the relatively intense levels of bcl-2 were expressed in both CD45RO+ and CD45RO- T-cell populations from normal subjects. This marked difference in bcl-2 expression of CD45RO+ T cells between acute IM and normal controls was also confirmed by Western blot analysis. Activated (CD45RO+) T cells with low bcl-2 expression, but not bcl-2-expressing CD45RO- T cells, in acute IM patients were found to die easily when cultured without added growth factors. However, in normal individuals, both CD45RO+ and CD45RO- T cells were relatively stable on culturing. These findings suggest that lack of bcl-2 expression by activated (CD45RO+) T cells in acute IM might be associated with their susceptibility to programmed cell death.

scholarly journals Apoptotic cell death of primed CD45RO+ T lymphocytes in Epstein-Barr virus-induced infectious mononucleosis

Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 452-458 ◽  
Author(s):  
T Uehara ◽  
T Miyawaki ◽  
K Ohta ◽  
Y Tamaru ◽  
T Yokoi ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Infectious Mononucleosis ◽  
Epstein Barr Virus ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Central Feature ◽  
Activated T Cells ◽  
Barr Virus ◽  
Epstein Barr

The expansion of activated T cells, characterized by the expression of CD45RO as well as HLA-DR antigens, is a central feature in acute infectious mononucleosis (IM) induced by primary infection of Epstein- Barr virus (EBV). However, the fate of these activated T cells in this disease is not clearly understood. We found that, on simple culture, a large proportion of T cells isolated from acute IM patients died rapidly, but only a few T cells from normal individuals did. Morphologic observations and DNA fragmentation analysis showed that the loss of viability of IM T cells after incubation was mediated by apoptosis. IM T cells undergoing apoptosis resided exclusively in the CD45RO+ populations of both CD4+ and CD8+ T cells, most of which were shown to coexpress apoptosis-related Fas antigen. Some cytokines such as interleukin-2 (IL-2), IL-5, and IL-6 could rescue IM T cells from apoptotic cell death. The results seemed to imply that most of primed (CD45RO+) T cells in acute IM might be subject to apoptotic cell death, possibly when leaving from the local sites actively producing certain soluble factors required for their survival. Our studies suggest the programmed cell death of peripheral mature T cells as a mechanism of antigen-driven selection.

scholarly journals Apoptotic cell death of primed CD45RO+ T lymphocytes in Epstein-Barr virus-induced infectious mononucleosis

Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 452-458 ◽  
Author(s):  
T Uehara ◽  
T Miyawaki ◽  
K Ohta ◽  
Y Tamaru ◽  
T Yokoi ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Infectious Mononucleosis ◽  
Epstein Barr Virus ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Central Feature ◽  
Activated T Cells ◽  
Barr Virus ◽  
Epstein Barr

Abstract The expansion of activated T cells, characterized by the expression of CD45RO as well as HLA-DR antigens, is a central feature in acute infectious mononucleosis (IM) induced by primary infection of Epstein- Barr virus (EBV). However, the fate of these activated T cells in this disease is not clearly understood. We found that, on simple culture, a large proportion of T cells isolated from acute IM patients died rapidly, but only a few T cells from normal individuals did. Morphologic observations and DNA fragmentation analysis showed that the loss of viability of IM T cells after incubation was mediated by apoptosis. IM T cells undergoing apoptosis resided exclusively in the CD45RO+ populations of both CD4+ and CD8+ T cells, most of which were shown to coexpress apoptosis-related Fas antigen. Some cytokines such as interleukin-2 (IL-2), IL-5, and IL-6 could rescue IM T cells from apoptotic cell death. The results seemed to imply that most of primed (CD45RO+) T cells in acute IM might be subject to apoptotic cell death, possibly when leaving from the local sites actively producing certain soluble factors required for their survival. Our studies suggest the programmed cell death of peripheral mature T cells as a mechanism of antigen-driven selection.

scholarly journals Response to Programmed Cell Death-1 Blockade in a Murine Melanoma Syngeneic Model Requires Costimulation, CD4, and CD8 T Cells

2016 ◽  
Vol 4 (10) ◽  
pp. 845-857 ◽  
Author(s):  
Blanca Homet Moreno ◽  
Jesse M. Zaretsky ◽  
Angel Garcia-Diaz ◽  
Jennifer Tsoi ◽  
Giulia Parisi ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cd8 T Cells ◽  
Murine Melanoma ◽  
Programmed Cell Death 1 ◽  
Syngeneic Model

scholarly journals Serum-derived exosomes promote CD8+ T cells to overexpress PD-1, affecting the prognosis of hypopharyngeal carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qian Gao ◽  
Hui-Ting Liu ◽  
Yu-Qin Xu ◽  
Lin Zhang ◽  
Yuan-Ru Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Programmed Cell Death ◽  
Cd8 T Cells ◽  
Poor Prognosis ◽  
Cell Function ◽  
Immune Escape ◽  
Cd8 T Cell ◽  
Serum Exosomes

Abstract Background Hypopharyngeal cancer (HPC) is associated with a poor prognosis and a high recurrence rate. Immune escape is one of the reasons for the poor prognosis of malignant tumors. Programmed cell death ligand 1 (PD-L1) and programmed cell death-1 (PD-1) have been shown to play important roles in immune escape. However, the role of PD-1/PD-L1 in HPC remains unclear. In this experiment, we investigated the effect of exosomes from HPC patient serum on CD8+ T cell function and PD-1/PD-L1 expression and, thus, on prognosis. We hope to provide guidance for the identification of new targets for HPC immunotherapy. Methods PD-1 and CD8 expression in 71 HPC tissues and 16 paracarcinoma tissues was detected by immunohistochemistry. Concurrently, the clinicopathological data of the patients were obtained to conduct correlation analysis. Exosomes were isolated from serum and then identified by Western blotting (WB), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Flow cytometry was used to assess the activity of CD8+ T cells after exosome stimulation. The effects of exosomes on the ability of CD8+ T cells to kill FaDu cells were assessed by CCK-8 assay. The expression of IL-10 and TGF-β1 was measured by enzyme-linked immunosorbent assay (ELISA). PD-L1 expression in HPC tissue samples was evaluated by immunohistochemistry, and the relationship between PD-1/PD-L1 expression and prognosis was investigated with patient specimens. Results PD-1 expression was significantly upregulated on CD8+ T cells in tumor tissues compared with those in normal tissues. The overall survival (OS) and disease-free survival (DFS) of PD-1-overexpressing patients were decreased. Serum exosomes from patients can elevate PD-1 expression on CD8+ T cells and suppress their killing capacity and secretory function. The rate of positive PD-L1 expression was increased in HPC tissues compared with paracancerous tissues. The DFS and OS of the PD-1(+)-PD-L1(+) group were significantly lower than those of the PD-1(−)-PD-L1(−) group. Conclusion Our findings indicate that serum exosomes from HPC patients can inhibit CD8+ T cell function and that the PD-1-PD-L1 pathway plays an important role in the immune escape of HPC. Exosomes combined with immunotherapy may guide the treatment of patients with advanced disease in the future.

scholarly journals Mice lacking Programmed cell death-1 show a role for CD8+ T cells in long-term immunity against blood-stage malaria

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Joshua M. Horne-Debets ◽  
Deshapriya S. Karunarathne ◽  
Rebecca J. Faleiro ◽  
Chek Meng Poh ◽  
Laurent Renia ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cd8 T Cells ◽  
Blood Stage ◽  
Programmed Cell Death 1 ◽  
Blood Stage Malaria

scholarly journals Comprehensive analysis of cutaneous and uveal melanoma liver metastases

2020 ◽  
Vol 8 (2) ◽  
pp. e001501
Author(s):  
Esmee P Hoefsmit ◽  
Elisa A Rozeman ◽  
Trieu My Van ◽  
Petros Dimitriadis ◽  
Oscar Krijgsman ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Liver Metastases ◽  
Uveal Melanoma ◽  
Cd8 T Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Metastatic Site ◽  
Immune Infiltration

BackgroundThe profound disparity in response to immune checkpoint blockade (ICB) by cutaneous melanoma (CM) and uveal melanoma (UM) patients is not well understood. Therefore, we characterized metastases of CM and UM from the same metastatic site (liver), in order to dissect the potential underlying mechanism in differential response on ICB.MethodsTumor liver samples from CM (n=38) and UM (n=28) patients were analyzed at the genomic (whole exome sequencing), transcriptional (RNA sequencing) and protein (immunohistochemistry and GeoMx Digital Spatial Profiling) level.ResultsComparison of CM and UM metastases from the same metastatic site revealed that, although originating from the same melanocyte lineage, CM and UM differed in somatic mutation profile, copy number profile, tumor mutational burden (TMB) and consequently predicted neoantigens. A higher melanin content and higher expression of the melanoma differentiation antigen MelanA was observed in liver metastases of UM patients. No difference in B2M and human leukocyte antigen-DR (HLA-DR) expression was observed. A higher expression of programmed cell death ligand 1 (PD-L1) was found in CM compared with UM liver metastases, although the majority of CM and UM liver metastases lacked PD-L1 expression. There was no difference in the extent of immune infiltration observed between CM and UM metastases, with the exception of a higher expression of CD163 (p<0.0001) in CM liver samples. While the extent of immune infiltration was similar for CM and UM metastases, the ratio of exhausted CD8 T cells to cytotoxic T cells, to total CD8 T cells and to Th1 cells, was significantly higher in UM metastases.ConclusionsWhile TMB was different between CM and UM metastases, tumor immune infiltration was similar. The greater dependency on PD-L1 as an immune checkpoint in CM and the identification of higher exhaustion ratios in UM may both serve as explanations for the difference in response to ICB. Consequently, in order to improve current treatment for metastatic UM, reversal of T cell exhaustion beyond programmed cell death 1 blockade should be considered.

Functional Significance of Adhesion Molecules in Fas-Dependent Apoptotic Cell Death Induced by Interleukin-2-Activated T Cells

1998 ◽  
Vol 27 (4-5) ◽  
pp. 309-322 ◽  
Author(s):  
Yan-Wen Zhou ◽  
Yoshihiro Komada ◽  
Hiroto Inaba ◽  
Takao Deguchi ◽  
Kenji Sugiyama ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Adhesion Molecules ◽  
Functional Significance ◽  
Apoptotic Cell ◽  
Interleukin 2 ◽  
Apoptotic Cell Death ◽  
Activated T Cells

scholarly journals CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells.

1996 ◽  
Vol 183 (6) ◽  
pp. 2533-2540 ◽  
Author(s):  
M F Krummel ◽  
J P Allison
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Cycle Progression ◽  
Cell Activation ◽  
Apoptotic Cell ◽  
Activated T Cells ◽  
Activated State

While interactions between CD28 and members of the B7 family costimulate and enhance T cell responses, recent evidence indicates that the CD28 homologue CTLA-4 plays a downregulatory role. The mechanism by which this occurs is not clear, but it has been suggested that CTLA-4 terminates ongoing responses of activated T cells, perhaps by induction of apoptosis. Here we demonstrate that CTLA-4 engagement by antibody cross-linking or binding to B7 inhibits proliferation and accumulation of the primary T cell growth factor, IL-2, by cells stimulated with anti-CD3 and anti-CD28. This inhibition is not a result of enhanced cell death. Rather it appears to result from restriction of transition from the G1 to the S phase of the cell cycle. Our observation that upregulation of both the IL-2R alpha chain and the CD69 activation antigen are inhibited by CTLA-4 engagement supplies further evidence that CTLA-4 restricts the progression of T cells to an activated state. Together this data demonstrates that CTLA-4 can regulate T cell activation in the absence of induction of apoptotic cell death.

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