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

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.

Download Full-text

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

Blood ◽

10.1182/blood.v80.2.452.452 ◽

1992 ◽

Vol 80 (2) ◽

pp. 452-458 ◽

Cited By ~ 133

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.

Download Full-text

Flow Cytometry and FTIR Spectroscopy for Detection of Early Apoptosis in Human T Cells

Proceedings ◽

10.3390/proceedings2251558 ◽

2018 ◽

Vol 2 (25) ◽

pp. 1558 ◽

Cited By ~ 1

Author(s):

Günnur Güler ◽

Ayten Nalbant

Keyword(s):

Flow Cytometry ◽

T Cells ◽

Cell Death ◽

Ftir Spectroscopy ◽

Apoptotic Cell ◽

Annexin V ◽

Apoptotic Cell Death ◽

Biochemical Changes ◽

Human T Cells ◽

Early Apoptosis

Apoptosis, a programmed cell death, has a vital role in various cellular processes. Apoptotic cells exhibit morphological and biochemical changes, detected by a variety of assays (caspases, mitochondrial dyes, DNA laddering). Flow cytometry is a powerful tool for detection of apoptotic cell death and allows information about the cell size and molecules associated with cell-bound antibodies. Recently, Fourier transform infrared (FTIR) spectroscopy as rapid and low-cost tool has been extensively used for cellular studies, providing information on cellular structures. The aim of this study was to detect early apoptosis and obtain further insights into the capability of FTIR spectroscopy, comparing the results with flow cytometry. In this study, apoptotic cell death was induced in human Jurkat T cells with Camptothecin (CPT), a DNA topoisomerase I inhibitor. Cells were cultured with 4µM CPT in RPMI (with 5% FCS) for 24 h. Immunoflourescence labeling for multicolor flow cytometry was accomplished with Annexin V concomitantly with 7-AAD. The same cells were also analyzed with ATR-FTIR spectroscopy. Flow cytometry data represents that the cells are Annexin V positive but 7AAD negative. This indicates that cells are in the early apoptotic stage, only externalization of phosphatidylserine exists on the plasma membrane. FTIR data reveals that membrane phospholipids and proteins undergo changes; fatty acid acyl chains are disordered and increased in mobility after treatment, which result from the early apoptosis process after CPT-treatment, confirmed by the flow cytometry. A combined study of flow cytometry and FTIR spectroscopy for analysis of apoptosis in human T cells exhibited compatible and complementary results. Existence of biophysical and biochemical changes in T cells after treatment were also demonstrated.

Download Full-text

Infection and Apoptotic Cell Death of CD4+T Cells during an Immune Response to HIV-1-Pulsed Dendritic Cells

AIDS Research and Human Retroviruses ◽

10.1089/aid.1994.10.61 ◽

1994 ◽

Vol 10 (1) ◽

pp. 61-71 ◽

Cited By ~ 75

Author(s):

P. U. CAMERON ◽

M. POPE ◽

S. GEZELTER ◽

R. M. STEINMAN

Keyword(s):

Immune Response ◽

T Cells ◽

Cell Death ◽

Dendritic Cells ◽

Cd4 T Cells ◽

Apoptotic Cell ◽

Apoptotic Cell Death ◽

Hiv 1

Download Full-text

Immunological unresponsiveness and apoptotic cell death of T cells in measles virus infection

Pediatrics International ◽

10.1111/j.1442-200x.1995.tb03320.x ◽

1995 ◽

Vol 37 (3) ◽

pp. 308-314 ◽

Cited By ~ 15

Author(s):

MICHAEL MARK ADDAE ◽

YOSHIHIRO KOMADA ◽

XAO-LI ZHANG ◽

MINORU SAKURAI

Keyword(s):

T Cells ◽

Cell Death ◽

Virus Infection ◽

Measles Virus ◽

Apoptotic Cell ◽

Apoptotic Cell Death

Download Full-text

Doxycycline is an NF-κB inhibitor that induces apoptotic cell death in malignant T-cells

Oncotarget ◽

10.18632/oncotarget.12488 ◽

2016 ◽

Vol 7 (46) ◽

pp. 75954-75967 ◽

Cited By ~ 19

Author(s):

Carolina V. Alexander-Savino ◽

Matthew S. Hayden ◽

Christopher Richardson ◽

Jiyong Zhao ◽

Brian Poligone

Keyword(s):

T Cells ◽

Cell Death ◽

Apoptotic Cell ◽

Apoptotic Cell Death ◽

Malignant T Cells

Download Full-text

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

Journal of Experimental Medicine ◽

10.1084/jem.183.6.2533 ◽

1996 ◽

Vol 183 (6) ◽

pp. 2533-2540 ◽

Cited By ~ 604

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.

Download Full-text

The significance of low bcl-2 expression by CD45RO T cells in normal individuals and patients with acute viral infections. The role of apoptosis in T cell memory.

Journal of Experimental Medicine ◽

10.1084/jem.178.2.427 ◽

1993 ◽

Vol 178 (2) ◽

pp. 427-438 ◽

Cited By ~ 225

Author(s):

A N Akbar ◽

N Borthwick ◽

M Salmon ◽

W Gombert ◽

M Bofill ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Viral Infections ◽

Apoptotic Cell ◽

Interleukin 2 ◽

Lymphoid Cells ◽

T Cell Memory ◽

Varicella Zoster Virus Infection ◽

Cell Memory ◽

Activated T Cells

The bcl-2 gene product has been shown to prevent apoptotic cell death. We have now investigated the bcl-2 protein expression by resting and activated mature T cell populations. Freshly isolated CD45RO+ T cells within CD4+ and CD8+ subsets expressed significantly less bcl-2 than CD45RO- (CD45RA+) T cells (p < 0.001). When CD45RA+ T cells within both CD4+ and CD8+ subsets were activated in vitro, the transition to CD45RO phenotype was associated with a decrease in bcl-2 expression. Patients with acute viral infections such as infectious mononucleosis caused by Epstein-Barr virus infections or chickenpox, resulting from varicella zoster virus infection, had circulating populations of activated CD45RO+ T cells which also showed low bcl-2 expression. In these patients, a significant correlation was seen between low bcl-2 expression by activated T cells and their apoptosis in culture (r = 0.94, p < 0.001). These results suggest that the primary activation of T cells leads to the expansion of a population that is destined to perish unless rescued by some extrinsic event. Thus the suicide of CD45RO+ T cells could be prevented by the addition of interleukin 2 to the culture medium which resulted in a concomitant increase in the bcl-2 expression of these cells. Alternatively, apoptosis was also prevented by coculturing the activated T lymphocytes with fibroblasts, which maintained the viability of lymphoid cells in a restinglike state but with low bcl-2 expression. The paradox that the CD45RO+ population contains the primed/memory T cell pool yet expresses low bcl-2 and is susceptible to apoptosis can be reconciled by the observations that maintenance of T cell memory may be dependent on the continuous restimulation of T cells, which increases their bcl-2 expression. Furthermore, the propensity of CD45RO+ T cells to extravasate may facilitate encounter with fibroblast-like cells in tissue stroma and thus be an important additional factor which promotes the survival of selected primed/memory T cells in vivo.

Download Full-text

Upregulated TNFR Family Member Insufficient to Promote Apoptotic Cell Death in T Helper 17 Cells

Proceedings ◽

10.3390/proceedings2251526 ◽

2018 ◽

Vol 2 (25) ◽

pp. 1526

Author(s):

Tufan Utku Çalışkan ◽

Ayten Nalbant

Keyword(s):

T Cells ◽

Cell Death ◽

Cd4 T Cells ◽

Th17 Cells ◽

Apoptotic Cell ◽

B Cell Lymphoma ◽

Apoptotic Cell Death ◽

T Helper ◽

T Helper 17 ◽

T Helper 17 Cells

Fas is the receptor of tumor necrosis family receptors (TNFR) and involves in apoptosis. Since discovery of T helper 17 cells (Th17) in 2005, which are defined as a new type of helper T cells, it has become clear that the dysregulated function Th17 cells and their cytokines could contribute to pathology of diseases including autoimmune diseases and cancer. There is not much known about apoptotic and survival mechanisms of Th17 cells in the literature. Therefore, the players of apoptotic cell death in Th17 cells were investigated in the study. To carry out designed experiments, venous blood were drawn from the healthy volunteers with approval from the Noninvasive Ethics Committee. Peripheral blood mononuclear cells (PBMCs) were isolated from blood with Ficoll separation method. The naïve CD4+ T cells were sorted from the PBMC. Sorted naive T cells were cultured under Th17 polarizing conditions. The activation, differentiation and apoptosis related molecules of cultured cells were monitored by Flow cytometry. Data showed that naive CD4+ T cells were activated and differentiated into Th17 cells. Activated Th17 cells were Fas positive. Activated, Fas positive Th17 cells did not underwent significant plasma membrane changes. Furthermore, it was also observed that there was not much change in the Bcl-2 protein level. Bcl-2 protein is belongs to B-cell-lymphoma-2 (Bcl-2) family proteins and is major regulator of intrinsic apoptotic pathway as promoting cell survival. In addition to that the expression of Bclx-L, is an anti-apoptotic protein, were increased in these cells. Data indicates that Th17 cells (under Th17 polarization condition) were increased expression of anti-apoptotic Bcl-2 family members.

Download Full-text