Molecular Mechanisms of Apoptosis in Naive and Memory Human T Cell Subsets

2019 ◽  
pp. 1139-1159
Author(s):  
Sudhir Gupta ◽  
Ankmalika Gupta
Blood ◽  
2005 ◽  
Vol 106 (10) ◽  
pp. 3440-3448 ◽  
Author(s):  
Mark S. Sundrud ◽  
Scott E. VanCompernolle ◽  
Karla A. Eger ◽  
Tullia C. Bruno ◽  
Arun Subramaniam ◽  
...  

AbstractCC chemokine receptor 5 (CCR5) is the major HIV-1 coreceptor and its expression levels are a critical determinant of HIV-1 infection. However, the molecular mechanisms of CCR5 regulation in primary targets of HIV-1 remain unknown. Despite binding to conserved DNA elements, we show that the transcription factors GATA binding protein 1 (GATA-1) and GATA-3 differentially suppress the expression of CCR5 in stem-cell–derived dendritic cells and primary human T-cell subsets. In addition, GATA-1 expression was also more potent than GATA-3 in suppressing T helper 1 (Th1)–associated genes, interferon-γ (IFNγ), and CXC chemokine receptor-3 (CXCR3). GATA-1, but not GATA-3, potently suppressed CCR5 transcription, thereby rendering human T cells resistant to CCR5-tropic HIV-1 infection. However, GATA-1 could also serve as a surrogate for GATA-3 in its canonic role of programming Th2 gene expression. These findings provide insight into GATA-3–mediated gene regulation during T-cell differentiation. Importantly, decoding the mechanisms of GATA-1–mediated repression of CCR5 may offer an opportunity to develop novel approaches to inhibit CCR5 expression in T cells.


1984 ◽  
Vol 72 (3) ◽  
pp. 213-214 ◽  
Author(s):  
J. Dufer ◽  
J. Bernard
Keyword(s):  
T Cell ◽  

Blood ◽  
1982 ◽  
Vol 59 (1) ◽  
pp. 198-201 ◽  
Author(s):  
JJ Hooks ◽  
BF Haynes ◽  
B Detrick-Hooks ◽  
LF Diehl ◽  
TL Gerrard ◽  
...  

Abstract We report a patient with a disease characterized by proliferation of T cells with Fc receptors for IgG (TG). However, unlike lymphoid cells from normal individuals or from patients with other lymphoid malignancies, the patient's lymphocytes spontaneously produced gamma interferon (IFN-gamma) in vitro. The peripheral lymphocytes consisted of 95% TG cells, which exhibited the morphological characteristics of T- cell chronic lymphocytic leukemia (CLL) and were normal on cytochemical and chromosome analysis. The majority of TG cells were OKT3+, OKT8+, and OKT4-, 3A1-. These cells failed to express suppressor cell activity and displayed depressed levels of natural killer activity, but mediated antibody-dependent cell-mediated cytotoxicity. The spontaneous production of IFN-gamma by human peripheral lymphoid cells as demonstrated in this study may serve as a probe for studying the relationship between IFN-gamma and the proliferation of human T-cell subsets.


2007 ◽  
Vol 179 (11) ◽  
pp. 7406-7414 ◽  
Author(s):  
Victor Appay ◽  
Andreas Bosio ◽  
Stefanie Lokan ◽  
Yvonne Wiencek ◽  
Christian Biervert ◽  
...  

Blood ◽  
1979 ◽  
Vol 53 (6) ◽  
pp. 1066-1075 ◽  
Author(s):  
EL Reinherz ◽  
LM Nadler ◽  
DS Rosenthal ◽  
WC Moloney ◽  
SF Schlossman

Abstract Circulating peripheral blood tumor cells in four cases of chronic lymphoproliferative disease were immunologically characterized. By the use of T-cell-specific heteroantisera and indirect immunofluorescence, all were shown to involve proliferation of malignant T cells. Three cases demonstrated morphologic and clinical features consistent with chronic lymphocytic leukemia (CLL), and one case presented as a lymphosarcoma cell leukemia. Antisera specific for normal human T-cell subsets defined the malignant T cells in each case as arising from the TH2--subset. This subset normally constitutes approximately 80% of human peripheral blood T cells. Terminal deoxynucleotidyl transferase (TdT) was not detected in any of the T-cell CLL cases, thus supporting the notion that T-cell CLL represents a malignancy of a mature phenotype. The one patient with lymphosarcoma whose tumor cells were TdT-positive subsequently developed T-cell acute lymphoblastic leukemia (ALL). Moreover, la-like antigen (p23,30) was detected on two of these tumor cell populations. In addition, it was shown that not all tumor cells were E-rosette-positive, since only cells from 3 of 4 patients were capable of forming spontaneous rosettes. These findings demonstrate that heteroantisera can provide an additional important tool for dissecting the heterogeneity of T-cell leukemias and for relating them to more differentiated normal T cells.


2020 ◽  
Vol 217 (9) ◽  
Author(s):  
Agata Cieslak ◽  
Guillaume Charbonnier ◽  
Melania Tesio ◽  
Eve-Lyne Mathieu ◽  
Mohamed Belhocine ◽  
...  

Cell differentiation is accompanied by epigenetic changes leading to precise lineage definition and cell identity. Here we present a comprehensive resource of epigenomic data of human T cell precursors along with an integrative analysis of other hematopoietic populations. Although T cell commitment is accompanied by large scale epigenetic changes, we observed that the majority of distal regulatory elements are constitutively unmethylated throughout T cell differentiation, irrespective of their activation status. Among these, the TCRA gene enhancer (Eα) is in an open and unmethylated chromatin structure well before activation. Integrative analyses revealed that the HOXA5-9 transcription factors repress the Eα enhancer at early stages of T cell differentiation, while their decommission is required for TCRA locus activation and enforced αβ T lineage differentiation. Remarkably, the HOXA-mediated repression of Eα is paralleled by the ectopic expression of homeodomain-related oncogenes in T cell acute lymphoblastic leukemia. These results highlight an analogous enhancer repression mechanism at play in normal and cancer conditions, but imposing distinct developmental constraints.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3313-3313
Author(s):  
J. Joseph Melenhorst ◽  
Josette Zeilah ◽  
Edgardo Sosa ◽  
Dean Follmann ◽  
Nancy F. Hensel ◽  
...  

Abstract Human T cell development occurs in two waves of development and proliferation: first, early T cells expressing the TCRb chain but not the α-chain are selected for functional TCRβ protein independent of HLA recognition, a process called β-selection; second, thymocytes expressing both the α- and β-TCR are selected for intermediate affinity for self-MHC/ self-peptide complex. This latter process is referred to as positive selection. We sought to determine whether the peripheral TCRVβ frequencies in the naïve T cell repertoire start off at a fixed rank order with minimal skewing as would be expected from a predominantly β-selected repertoire. A total of 22 TCRVβ proteins was quantitated by flow cytometry in a group of 20 unselected umbilical cord blood (UCB) samples (a kind gift from Dr. P. Rubinstein, NY Blood Center, NY), consisting of >80% naïve T cells as defined by CD27+CD45RA+ staining in CD4+ and CD8+ cells. A common rank order of TCRVβ protein frequencies was found in both CD4 and CD8 T cell subsets (figure 1). Median TCRVβ frequencies in CD4 and in CD8 cells of UCB were statistically not significantly different from the frequencies in adult donor CD4 and CD8 cells (Wilcoxon signed rank test; p > 0.2). Furthermore, the percentages of CD4 cells expressing a particular Vβ correlated significantly in CD8 cells (figure 2) with some Vβ proteins being predominantly expressed by either CD4 (Vβ2, Vβ5.1) or CD8 (Vβ14, Vβ7) cells. Our data therefore conform to the prediction that the TCRVβ frequencies are dominantly shaped by β-selection, and not by interactions of the αβTCR/ co-receptor with MHC/ antigen complexes during thymic selection. Figure 1. TCRBV in UCB CD4+ (top) and CD8+ (bottom) T cells Figure 1. TCRBV in UCB CD4+ (top) and CD8+ (bottom) T cells Figure 2. Comparison of TCRBV protein expression frequencies in CD4 and CD8 cells of UCB Figure 2. Comparison of TCRBV protein expression frequencies in CD4 and CD8 cells of UCB


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