scholarly journals Properties of transcription factors regulating interleukin-2 gene transcription through the NFAT binding site in untreated or drug- treated naive and memory T-helper cells

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2612-2621 ◽  
Author(s):  
A Mouzaki ◽  
D Rungger
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Binding Site ◽  
T Helper Cells ◽  
Interleukin 2 ◽  
Jurkat Cells ◽  
Memory Cells ◽  
T Helper ◽  
Binding Studies ◽  
Helper Cells

Abstract Combining in vitro DNA binding studies and functional transcription assays in the Xenopus oocyte, we have tested the presence and functional state of transcription factors controlling the interleukin-2 (IL-2) promoter through the NFAT binding site. In naive T-helper cells, the IL-2 gene is repressed by a silencer. After first mitogenic stimulation, this silencer becomes undetectable while an activator is newly synthesized. In resting memory cells, the activator has low DNA- binding affinity and is located in the cytoplasm. However, no silencer is formed. Upon renewed cellular activation, this pre-existing activator is again targeted to the nucleus and regains function in promoting transcription. Cyclosporin A and FK506 act on two distinct levels of the IL-2 control mechanism. They prevent nuclear transport and reactivation of the performed activator in memory cells and, in naive cells, they render the silencer resistant to displacement by the activator. DNA-binding of silencer and activator from T-helper, and NFAT-1 from Jurkat cells, requires the same three G residues, but cross- linking analyses show differences in their constituent subunits. Supershift experiments show that the activator contains fra-2 and junD, whereas the silencer reacts with none of the antibodies tested.

scholarly journals Properties of transcription factors regulating interleukin-2 gene transcription through the NFAT binding site in untreated or drug- treated naive and memory T-helper cells

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2612-2621 ◽  
Author(s):  
A Mouzaki ◽  
D Rungger
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Binding Site ◽  
T Helper Cells ◽  
Interleukin 2 ◽  
Jurkat Cells ◽  
Memory Cells ◽  
T Helper ◽  
Binding Studies ◽  
Helper Cells

Combining in vitro DNA binding studies and functional transcription assays in the Xenopus oocyte, we have tested the presence and functional state of transcription factors controlling the interleukin-2 (IL-2) promoter through the NFAT binding site. In naive T-helper cells, the IL-2 gene is repressed by a silencer. After first mitogenic stimulation, this silencer becomes undetectable while an activator is newly synthesized. In resting memory cells, the activator has low DNA- binding affinity and is located in the cytoplasm. However, no silencer is formed. Upon renewed cellular activation, this pre-existing activator is again targeted to the nucleus and regains function in promoting transcription. Cyclosporin A and FK506 act on two distinct levels of the IL-2 control mechanism. They prevent nuclear transport and reactivation of the performed activator in memory cells and, in naive cells, they render the silencer resistant to displacement by the activator. DNA-binding of silencer and activator from T-helper, and NFAT-1 from Jurkat cells, requires the same three G residues, but cross- linking analyses show differences in their constituent subunits. Supershift experiments show that the activator contains fra-2 and junD, whereas the silencer reacts with none of the antibodies tested.

scholarly journals Regulatory idiotypes. T helper cells recognize a shared VH idiotope on phosphorylcholine-specific antibodies.

1982 ◽  
Vol 156 (2) ◽  
pp. 539-549 ◽  
Author(s):  
K Gleason ◽  
H Köhler
Keyword(s):  
T Cells ◽  
B Cell ◽  
Binding Site ◽  
T Helper Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
T Helper ◽  
Binding Studies ◽  
Heavy Chains ◽  
Helper Cells ◽  
Myeloma Proteins

Priming of BALB/c mice with phosphorylcholine-hemocyanin (PC-Hy) induces T helper cells that are detected in splenic fragment cultures responding to immunization with trinitrophenylated PC-binding myeloma proteins, TEPC 15 (TNP-T15) and MOPC 167 (TNP-M167). Trinitrophenylation did not alter the binding site, idiotype, or isotype of the antibodies as demonstrated by binding studies. To assay idiotype-recognizing helper cells, Ly-2.2-depleted T cells from PC-Hy-primed donor mice were transferred to syngeneic athymic mice. Splenic anti-trinitrophenol fragment cultures were prepared from the nude recipients, and the response to TNP-T15 and TNP-M167 was measured by enzyme-linked immunosorbent assay. The number of responding fragments is dependent on the number of transferred primed T cells. The homing efficiency of 51Cr-labeled helper cells into the spleen of nude recipients was determined. The frequencies of T helper cells taken from PC-Hy-primed donors required for a B cell response to TNP-T15 or TNP-M167 were indistinguishable. The fine specificity of the anti-PC idiotype-recognizing T helper cells was studied by adding hapten (PC) or unconjugated myeloma proteins to fragment cultures as inhibitors at the time of immunization. PC and PC-bovine serum albumin, as well as T15 and M167, inhibited the helper function in vitro. Furthermore, free heavy chains of T15 and M167 partially inhibited T help, but free light chains of both idiotypes had no effect. These findings collectively show that T helper cells, induced by priming with antigen, recognize a shared idiotypic determination on T15 and M167 that is part of the PC binding site. The heavy chains of T15 and M167 appears to be the major structural component of this determinant. Evidently, T helper cells can recognize a shared determinant that is present on idiotypically different myeloma proteins. This determinant appears to be conserved throughout evolutionary and somatic mutations. The role of this shared, binding site-related idiotypic determinant as a regulatory idiotype in T-B cell interaction is discussed.

scholarly journals Increased antiplatelet T helper lymphocyte reactivity in patients with autoimmune thrombocytopenia

Blood ◽  
1991 ◽  
Vol 78 (10) ◽  
pp. 2619-2625 ◽  
Author(s):  
JW Semple ◽  
J Freedman
Keyword(s):  
Peripheral Blood ◽  
T Helper Cells ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Autoimmune Disorder ◽  
T Helper ◽  
Phenotypic Analysis ◽  
Activated T Cells ◽  
Peripheral Blood Mononuclear ◽  
Helper Cells

Chronic autoimmune thrombocytopenic purpura (ATP) is a common hematologic disorder in which platelet-specific autoantibodies bind to platelets and enhance their destruction by the reticuloendothelial system. While there has been considerable investigation of the humoral immune abnormalities in ATP, little work has been performed on the cellular immunoregulatory aspects of this autoimmune disorder. We describe here that patients with ATP have lymphocytes that proliferate normally when stimulated by mitogens. However, when stimulated by normal control platelets in 7-day antigen-presenting cell cultures, peripheral blood mononuclear cells (PBMC) from patients with ATP proliferate at significantly higher levels (P less than .001) and their lymphocytes secrete significantly higher amounts of interleukin-2 (IL- 2) (P less than .001) than do lymphocytes from control subjects. Depletion studies with monoclonal anti-CD8 and complement did not reduce the proliferative capacity of the responding PBMC population, indicating that CD4+ T-helper cells may be responsible for the response. Phenotypic analysis of peripheral blood lymphocyte subsets from patients with ATP showed that there was a significant reduction in CD4+Leu8+ T suppressor-inducer cells (P less than .001) and a concomitant increase in CD3+DR+ activated T cells (P less than .001) and CD19+ B cells (P less than .05). These data indicate that CD4+ T- helper cells from patients with ATP are stimulated by normal platelet antigen(s) to secrete IL-2 and may modulate the enhanced antiplatelet autoantibody response.

scholarly journals Mechanism of Follicular Helper T Cell Differentiation Regulated by Transcription Factors

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Long-Shan Ji ◽  
Xue-Hua Sun ◽  
Xin Zhang ◽  
Zhen-Hua Zhou ◽  
Zhuo Yu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Differentiation ◽  
B Cells ◽  
T Helper Cells ◽  
Molecular Mechanisms ◽  
Transcriptional Level ◽  
T Helper ◽  
Tfh Cells ◽  
Helper Cells ◽  
Follicular Helper

Helping B cells and antibody responses is a major function of CD4+T helper cells. Follicular helper T (Tfh) cells are identified as a subset of CD4+T helper cells, which is specialized in helping B cells in the germinal center reaction. Tfh cells express high levels of CXCR5, PD-1, IL-21, and other characteristic markers. Accumulating evidence has demonstrated that the dysregulation of Tfh cells is involved in infectious, inflammatory, and autoimmune diseases, including lymphocytic choriomeningitis virus (LCMV) infection, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), IgG4-related disease (IgG4-RD), Sjögren syndrome (SS), and type 1 diabetes (T1D). Activation of subset-specific transcription factors is the essential step for Tfh cell differentiation. The differentiation of Tfh cells is regulated by a complicated network of transcription factors, including positive factors (Bcl6, ATF-3, Batf, IRF4, c-Maf, and so on) and negative factors (Blimp-1, STAT5, IRF8, Bach2, and so on). The current knowledge underlying the molecular mechanisms of Tfh cell differentiation at the transcriptional level is summarized in this paper, which will provide many perspectives to explore the pathogenesis and treatment of the relevant immune diseases.

scholarly journals CDw60: a marker for human CD8+ T helper cells.

1994 ◽  
Vol 179 (4) ◽  
pp. 1385-1390 ◽  
Author(s):  
E P Rieber ◽  
G Rank
Keyword(s):  
T Cell ◽  
T Helper Cells ◽  
Interleukin 2 ◽  
Cell Subset ◽  
Cd8 T Cell ◽  
Pokeweed Mitogen ◽  
B Cell Differentiation ◽  
T Helper ◽  
Cd8 Cells ◽  
Helper Cells

The existence of helper cells among the CD8+ T cell subset has been recognized for a long time. However, the phenotype of these cells has remained elusive. In this study, we provide evidence that the expression of the CDw60 antigen on human CD8+ T cell allows one to distinguish between CD8+ T helper cells and CD8+ T cells with cytotoxic and suppressor capacity. CDw60 monoclonal antibodies (mAb) recognize the 9-O-acetylated disialosyl group on ganglioside GD3 expressed on 20-40% of CD8+ cells. By use of the direct and indirect mAb-rosetting technique, we were able to isolate the CDw60+CD8+ and CDw60-CD8+ cells at high purity. The alloantigen-specific cytotoxic activity of CD8+ cells resided entirely in the CDw60- population. Helper and suppressor capacity of both CD8 subsets was assayed by the pokeweed mitogen-induced differentiation of B cells into immunoglobulin-secreting cells. These studies clearly indicate that the CDw60+CD8+ subset provided substantial help to B lymphocytes, whereas the CD8+ cells with the CDw60- phenotype were suppressing B cell differentiation. Both subsets produced similar amounts of interleukin 2 (IL-2) after stimulation with phytohemagglutinin. Activation with phorbol myristate acetate in combination with Ca-ionophore induced IL-4 secretion in both populations, but preferentially in the CDw60+ subset, whereas the vast majority of interferon gamma was produced by the CDw60-CD8+ cells. When used in combination with other markers, CDw60 may prove to be useful in defining CD8+ subsets with reciprocal functional activities.

Chronic morphine treatment differentiates T helper cells to Th2 effector cells by modulating transcription factors GATA 3 and T-bet

2004 ◽  
Vol 147 (1-2) ◽  
pp. 78-81 ◽  
Author(s):  
Sabita Roy ◽  
Jinghua Wang ◽  
Sumandeep Gupta ◽  
Richard Charboneau ◽  
Horace H. Loh ◽  
...  
Keyword(s):  
Transcription Factors ◽  
T Helper Cells ◽  
T Helper ◽  
Morphine Treatment ◽  
Chronic Morphine ◽  
Effector Cells ◽  
Helper Cells ◽  
Chronic Morphine Treatment

scholarly journals Lack of enhanced T-helper cell function in uremic patients with circulating alloreactive antibodies.

1995 ◽  
Vol 5 (7) ◽  
pp. 1441-1450
Author(s):  
A Shoker ◽  
R Miller ◽  
R Uldall ◽  
E Friedman ◽  
S Angra ◽  
...  
Keyword(s):  
T Helper Cells ◽  
Blood Lymphocyte ◽  
Cell Function ◽  
Interleukin 2 ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Cd4 Cells ◽  
Helper Cells ◽  
Uremic Patients

Some uremic patients with a history of blood transfusion, pregnancy, and previous transplantation maintain high levels of alloreactive cytotoxic antibodies in the absence of continuous exogenous allogenic stimuli and are thus considered sensitized to the major histocompatibility proteins. To differentiate into antibody-producing cells, B lymphocytes must interact with T-helper (CD4+) cells. Whether ongoing help from these cells is necessary for the B cells to continue producing cytotoxic alloreactive antibodies in these sensitized uremic patients is unknown. To gain insight into the cellular mechanisms that are associated with sustained alloantibody production, T cell activation markers were measured and specific and nonspecific T-helper cell function was studied in three uremic groups with different levels of panel reactive antibodies: 10 patients whose sera reacted to more than 80% of a panel of normal lymphocytes for at least 6 months before the study were highly sensitized, 20 patients whose sera reacted to less than 80% of the panel were moderately sensitized, and 10 nonsensitized patients whose sera did not react to any cell on the panel. The number of total and activated T-helper cells was similar in the highly sensitized and nonsensitized patients. Peripheral blood lymphocyte proliferation in response to plant lectins, soluble OKT3, or alloantigens was similar in the three uremic groups. The spontaneous proliferation of pure T-helper cells and proliferative responses to immobilized OKT3 or alloantigens were also similar in highly sensitized and nonsensitized patients. Alloreactive interleukin-2-producing cell frequencies with pure CD4+ cells as responding cells were 771 +/- 77.9/10(6) cells in highly sensitized, 945 +/- 252/10(6) cells in nonsensitized, and 973 +/- 114/10(6) cells in controls (P = not significant). Panel reactive antibody levels did not correlate with any of the measures of T helper responses. There was a significant decrease of peripheral blood lymphocyte responses to alloantigens and anti-CD3 antibody in all uremic patients as compared with normals, suggesting a dysfunction in accessory cells that was quantitatively similar in sensitized and nonsensitized patients. In spite of the continuous production of alloantibodies by B cells, there is no evidence of either specific or nonspecific enhancement of T-helper cell function in sensitized patients. The absence of T cell immunity to alloantigens suggests that sustained activation of T-helper cells with subsequent interleukin-2 production is not necessary to maintain alloreactive B cell function.

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