scholarly journals Interleukin 2 receptor-targeted cytotoxicity. Interleukin 2 receptor-mediated action of a diphtheria toxin-related interleukin 2 fusion protein.

1988 ◽  
Vol 167 (2) ◽  
pp. 612-622 ◽  
Author(s):  
P Bacha ◽  
D P Williams ◽  
C Waters ◽  
J M Williams ◽  
J R Murphy ◽  
...  
Keyword(s):  
T Cells ◽  
Protein Synthesis ◽  
T Cell ◽  
Diphtheria Toxin ◽  
Interleukin 2 ◽  
Elongation Factor ◽  
High Affinity ◽  
Interleukin 2 Receptor ◽  
Human T Cell ◽  
Inhibition Of Protein Synthesis

The IL-2 toxin-mediated inhibition of protein synthesis in high affinity IL-2-R-positive murine and human T cell lines has been examined. Both excess free IL-2 and mAb to the Tac epitope of the p55 subunit of IL-2-R are shown to block the action of IL-2 toxin; whereas, agents that interact with other receptors or antigens on the T cell surface have no effect. We show that IL-2 toxin, like diphtheria toxin, must pass through an acidic vesicle in order to intoxicate target T cells. Finally, we demonstrate that the IL-2 toxin-mediated inhibition of protein synthesis in both human and murine T cells that bear the high affinity IL-2-R is due to the classic diphtheria toxin fragment A-catalyzed ADP ribosylation of elongation factor 2.

scholarly journals High-affinity receptor-mediated internalization and degradation of interleukin 2 in human T cells.

1986 ◽  
Vol 163 (3) ◽  
pp. 550-562 ◽  
Author(s):  
M Fujii ◽  
K Sugamura ◽  
K Sano ◽  
M Nakai ◽  
K Sugita ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Interleukin 2 ◽  
Culture Fluid ◽  
Type I ◽  
Temperature Dependent ◽  
High Affinity ◽  
Human T Cell ◽  
Human T Cells ◽  
High Affinity Receptor

Receptor-mediated internalization and degradation of IL-2 were investigated in cell lines carrying human T cell leukemia/lymphoma (lymphotrophic) virus type I (HTLV-I) and PHA-treated normal PBL. The HTLV-I-carrying cell lines ILT-Yan and TL-Mor, and the PBL expressed both high- and low-affinity IL-2-R. However, another HTLV-I-carrying T cell line, MT-1, expressed mainly low-affinity receptors. Greater than 50% of the IL-2 bound to high-affinity receptors was internalized within 10 min when these cells were incubated at 37 degrees C. The internalized IL-2 was rapidly degraded and the products were excreted into the culture fluid. The t1/2 of IL-2 degradation in these cells was estimated as 60-80 min at 37 degrees C. The internalization and degradation of IL-2 were both temperature dependent. Light-microscopic autoradiography with 3H-labeled IL-2 confirmed the internalization of IL-2, and suggested that some IL-2 might be carried to the nucleus.

Inhibition of Interleukin-2 Synthesis and Interleukin-2 Receptor α Expression on T Cells by a Cell-Free Factor Derived from a CD4+ Regulatory T Cell Clone

1993 ◽  
Vol 68 (3) ◽  
pp. 256-262 ◽  
Author(s):  
Takashi Okino ◽  
Nitya G. Chakraborty ◽  
Paul Stabach ◽  
Daniel R. Twardzik ◽  
Steven J. Padula ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cell ◽  
Cell Clone ◽  
Interleukin 2 ◽  
Interleukin 2 Receptor ◽  
T Cell Clone ◽  
A Cell

scholarly journals Inhibition or activation of human T cell receptor transfectants is controlled by defined, soluble antigen arrays.

1992 ◽  
Vol 176 (5) ◽  
pp. 1421-1430 ◽  
Author(s):  
D E Symer ◽  
R Z Dintzis ◽  
D J Diamond ◽  
H M Dintzis
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Jurkat Cells ◽  
Soluble Antigen ◽  
Human T Cell ◽  
Human T Cells ◽  
Binding Avidity

We present evidence that direct T cell receptor (TCR) occupancy by antigen can either activate or inhibit T cells, depending upon whether or not a threshold number of local TCRs are crosslinked by multivalent arrays of the antigen. Variants of Jurkat cells were previously transfected with TCR alpha and beta chains that bind fluorescein, yielding FL-TCR+ human T cells. The transfectants are activated upon binding soluble multivalent antigen arrays at concentrations well below those required for monovalent interactions. This activation, measured by calcium fluxes and interleukin 2 (IL-2) production, indicates the superior binding avidity of multivalent ligands. Smaller, less multivalent arrays do not activate the cells, but antagonize larger arrays, demonstrating that antigen can bind TCR as either agonist or antagonist. The balance between activation and inhibition depends upon antigen array size, ligand valence, and concentration, indicating that a threshold extent of receptor crosslinking, and not individual perturbations of single TCR, is required for activation by antigen. Approximately 100 stimulatory arrays specifically bind per FL-TCR+ cell at concentrations where IL-2 production is half-maximal.

scholarly journals Involvement of the interleukin 2 pathway in the rearrangement and expression of both alpha/beta and gamma/delta T cell receptor genes in human T cell precursors.

1988 ◽  
Vol 168 (6) ◽  
pp. 2231-2249 ◽  
Author(s):  
M L Toribio ◽  
A de la Hera ◽  
J Borst ◽  
M A Marcos ◽  
C Márquez ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Beta Chain ◽  
Gamma Delta ◽  
Human T Cell ◽  
Alpha Beta ◽  
A Minor

In this report, we have undertaken the phenotypic, functional and molecular characterization of a minor (less than 5%) subpopulation of adult thymocytes regarded as the earliest intrathymic T-cell precursors. Pro-T cells were immunoselected and shown to express different hematopoietic cell markers (CD45, CD38, CD7, CD5) and some activation-related molecules (4F2, Tr, HLA class II), but lack conventional T cell antigens (CD2-1-3-4-8-). TCR-gamma RNA messages are already expressed at this early ontogenic stage, while alpha and beta chain TCR genes remain in germline configuration. In vitro analyses of the growth requirements of pro-T cells demonstrated the involvement of the IL-2 pathway in promoting their proliferation and differentiation into CD3+ CD4+ or CD8+ mature thymocytes. Moreover, during the IL-2-mediated maturation process rearrangements and expression of both alpha and beta chain TCR genes occurred, and resulted in the acquisition of alpha/beta as well as gamma/delta (either disulphide-linked or non-disulphide-linked) heterodimeric TCR among the pro-T cell progeny.

scholarly journals Proliferation Response to Interleukin-2 and Jak/Stat Activation of T Cells Immortalized by Human T-Cell Lymphotropic Virus Type 1 Is Independent of Open Reading Frame I Expression

1999 ◽  
Vol 73 (11) ◽  
pp. 9642-9649 ◽  
Author(s):  
Nathaniel D. Collins ◽  
Celine D’Souza ◽  
Björn Albrecht ◽  
Michael D. Robek ◽  
Lee Ratner ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Virus Type ◽  
Interleukin 2 ◽  
Receptor Expression ◽  
Open Reading Frame ◽  
Reading Frame ◽  
Human T Cell

ABSTRACT Human T-cell lymphotropic virus type 1 (HTLV-1), a complex retrovirus, encodes a hydrophobic 12-kD protein from pX open reading frame (ORF) I that localizes to cellular endomembranes and contains four minimal SH3 binding motifs (PXXP). We have demonstrated the importance of ORF I expression in the establishment of infection and hypothesize that p12I has a role in T-cell activation. In this study, we tested interleukin-2 (IL-2) receptor expression, IL-2-mediated proliferation, and Jak/Stat activation in T-cell lines immortalized with either wild-type or ORF I mutant clones of HTLV-1. All cell lines exhibited typical patterns of T-cell markers and maintained mutation fidelity. No significant differences between cell lines were observed in IL-2 receptor chain (α, β, or γc) expression, in IL-2-mediated proliferation, or in IL-2-induced phosphorylated forms of Stat3, Stat5, Jak1, or Jak3. The expression of ORF I is more likely to play a role in early HTLV-1 infection, such as in the activation of quiescent T cells in vivo.

Differential regulation of T-cell growth by IL-2 and IL-15

Blood ◽  
2006 ◽  
Vol 108 (2) ◽  
pp. 600-608 ◽  
Author(s):  
Georgina H. Cornish ◽  
Linda V. Sinclair ◽  
Doreen A. Cantrell
Keyword(s):  
T Cells ◽  
Protein Synthesis ◽  
Amino Acid ◽  
T Cell ◽  
Cell Growth ◽  
De Novo ◽  
Cell Mass ◽  
Interleukin 2 ◽  
Amino Acid Uptake ◽  
Acid Uptake

Although interleukin 2 (IL-2) and IL-15 signal through the common gamma chain (γc) and through IL-2 receptor β–chain (CD122) subunits, they direct distinct physiologic and immunotherapeutic responses in T cells. The present study provides some insight into why IL-2 and IL-15 differentially regulate T-cell function by revealing that these cytokines are strikingly distinct in their ability to control protein synthesis and T-cell mass. IL-2 and IL-15 are shown to be equivalent mitogens for antigen-stimulated CD8+ T cells but not for equivalent growth factors. Antigen-primed T cells cannot autonomously maintain amino acid incorporation or de novo protein synthesis without exogenous cytokine stimulation. Both IL-2 and IL-15 induce amino acid uptake and protein synthesis in antigen-activated T cells; however, the IL-2 response is strikingly more potent than the IL-15 response. The differential action of IL-2 and IL-15 on amino acid uptake and protein synthesis is explained by temporal differences in signaling induced by these 2 cytokines. Hence, the present results show that cytokines that are equivalent mitogens can have different potency in terms of regulating protein synthesis and cell growth.

scholarly journals Thalidomide Costimulates Primary Human T Lymphocytes, Preferentially Inducing Proliferation, Cytokine Production, and Cytotoxic Responses in the CD8+ Subset

1998 ◽  
Vol 187 (11) ◽  
pp. 1885-1892 ◽  
Author(s):  
Patrick A.J. Haslett ◽  
Laura G. Corral ◽  
Matthew Albert ◽  
Gilla Kaplan
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interleukin 2 ◽  
Cell Subset ◽  
Cell Receptor ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
T Cell Subset ◽  
Human T Cell

The efficacy of thalidomide (α-phthalimido-glutarimide) therapy in leprosy patients with erythema nodosum leprosum is thought to be due to inhibition of tumor necrosis factor α. In other diseases reported to respond to thalidomide, the mechanism of action of the drug is unclear. We show that thalidomide is a potent costimulator of primary human T cells in vitro, synergizing with stimulation via the T cell receptor complex to increase interleukin 2–mediated T cell proliferation and interferon γ production. The costimulatory effect is greater on the CD8+ than the CD4+ T cell subset. The drug also increases the primary CD8+ cytotoxic T cell response induced by allogeneic dendritic cells in the absence of CD4+ T cells. Therefore, human T cell costimulation can be achieved pharmacologically with thalidomide, and preferentially in the CD8+ T cell subset.

scholarly journals T-cell death by apoptosis in vertically human immunodeficiency virus- infected children coincides with expansion of CD8+/interleukin-2 receptor-/HLA-DR+ T cells: sign of a possible role for herpes viruses as cofactors?

Blood ◽  
1995 ◽  
Vol 86 (4) ◽  
pp. 1400-1407 ◽  
Author(s):  
RP Lauener ◽  
S Huttner ◽  
M Buisson ◽  
JP Hossle ◽  
M Albisetti ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Hiv Infection ◽  
Interleukin 2 ◽  
Herpes Viruses ◽  
Interleukin 2 Receptor ◽  
Hla Dr ◽  
Immunodeficiency Virus

One mechanism proposed to play a role in T-cell depletion in human immunodeficiency virus (HIV) infection is apoptosis (activation-induced cell death). We assessed whether apoptosis is related to activation of T cells in vivo and its possible triggers. DNA was extracted from peripheral blood mononuclear cells (PBMC) taken from 16 vertically HIV- infected children and 9 HIV-negative children born to HIV-positive mothers (controls) and tested by agarose gel electrophoresis for the presence of DNA fragments specific for apoptosis. Signs of apoptosis were found on in vitro culture of PBMC from 12 of 16 HIV-infected children, but not in PBMC from the nine controls. Eleven of the 12 HIV- infected children with apoptosis showed an elevated (> 15%) proportion of CD3+/HLA-DR+ cells. This was due to an increased proportion of CD8+/HLA-DR+ cells, as shown in 7 of 7 further tested patients. In none of the probands an increased (> 5%) proportion of IL-2 receptor expressing CD3+ cells was found. T cells undergoing apoptosis were preferentially of the CD8+ phenotype. Expansion of circulating CD8+/interleukin-2 receptor (IL-2R)-/HLA-DR+ T cells is known to occur during active infection with herpes viruses. To investigate the possible role of herpes viral coinfections for apoptosis in HIV infection, we focused on Epstein-Barr virus (EBV) as an example for a herpes virus usually acquired during childhood. In 10 of 12 patients with apoptosis, we found increased levels of EBV genome in PBMC and/or tissues, indicating active EBV replication. By contrast, no increased burden of EBV was found in the four HIV-infected patients without apoptosis or in the controls. Our data indicate that in children the occurrence of apoptosis in HIV infection is closely related to activation of CD8+ T cells. Furthermore, primoinfection with or reactivation of herpes viruses, such as EBV, may substantially contribute to such T-cell activation and the ensuing apoptosis. Additional studies are warranted to evaluate the contribution of herpes virus-triggered apoptosis to the T-cell loss leading to the acquired immunodeficiency syndrome.

scholarly journals Monoclonal antibody defining a molecule possibly identical to the p75 subunit of interleukin 2 receptor.

1989 ◽  
Vol 169 (4) ◽  
pp. 1323-1332 ◽  
Author(s):  
T Takeshita ◽  
Y Goto ◽  
K Tada ◽  
K Nagata ◽  
H Asao ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Interleukin 2 ◽  
High Affinity ◽  
Human T Cell ◽  
Low Concentrations ◽  
High Concentrations ◽  
Dependent Growth ◽  
T Cell Lines

A mouse hybridoma cell line, TU27, producing an mAb was established. TU27 mAb reacted with various human and Gibbon ape T cell lines bearing the IL-2R p75 (IL-2Rp75), but not with cell lines expressing only Tac antigen, IL-2Rp55, and numbers of its binding sites on cell surfaces were similar to those of high-affinity IL-2R. Radioimmunoprecipitation with TU27 mAb defined a molecule with a molecular mass of 75 kD on the surface of IL-2Rp75 bearing cells. TU27 mAb completely blocked IL-2 binding to IL-2Rp75 and to the high-affinity IL-2R but not to IL-2Rp55 composing the low-affinity IL-2R. The IL-2-dependent growth of a human T cell line, ILT-Mat, was significantly inhibited by TU27 mAb only at low concentrations of IL-2, and combination of TU27 mAb and H-31 mAb specific for IL-2Rp55 completely inhibited the cell growth even at high concentrations of IL-2. These data strongly suggest that TU27 mAb is specific for the human IL-2Rp75.

Sign in / Sign up

Export Citation Format

Share Document