Interleukin 2 stimulates tyrosine phosphorylation in T cell membrane fractions

1989 ◽  
Vol 185 (2) ◽  
pp. 455-459 ◽  
Author(s):  
Jean-Pierre PIAU ◽  
Hiro WAKASUGI ◽  
Jacques BERTOGLIO ◽  
Thomas TURSZ ◽  
Didier FRADELIZI ◽  
...  
Author(s):  
Yanhua Li ◽  
Xia Zhang ◽  
Xiaohan Liu ◽  
Wei Pan ◽  
Na Li ◽  
...  

Chemotherapy is always ineffective against cancer metastasis due to the limited diffusion ability of passive agents into the internal tumor. Herein, we designed a mineralization strategy based on the multifunctional...


Blood ◽  
1994 ◽  
Vol 84 (4) ◽  
pp. 1182-1192 ◽  
Author(s):  
F Mentz ◽  
F Ouaaz ◽  
A Michel ◽  
C Blanc ◽  
P Herve ◽  
...  

Abstract In this study, we have investigated the ability of various cytokines to induce the maturation of acute lymphoblastic leukemia (T-ALL) cells with early T-cell phenotype. Leukemic blasts from 17 untreated T-ALL patients were assayed for their ability to acquire mature T-cell markers, CD3/T-cell receptor (TCR) in particular, after incubation with one or a combination of recombinant human interleukin-1 (IL-1), IL-2, IL-4, IL-7, and CD2-specific monoclonal antibody (MoAb). IL-7 or IL-2 induced the proliferation of some leukemic cells, whereas sequential cell treatment with CD2-MoAb and then IL-2 promoted CD3/TCR expression on nearly all CD2+ cells (15 of 16), except for 1 T-ALL that developed into CD3-CD16+CD56+ cells. Differentiation of T-ALL cells was also evidenced through the downregulation of CD34 precursor cell antigen, the generation of CD4+ and CD8+ cells from CD4+ CD8+ precursors, and the acquisition of mature T-cell functions. CD2 ligation induced a progressive increase of surface expression of IL-2 receptor alpha (IL- 2R alpha) and IL-2R beta and an accelerated in vitro death of leukemic cells. The ligation of IL-2R by IL-2 rescued T-ALL cells from death and promoted their progression toward more mature cells expressing extracellular CD3/TCR alpha beta complexes. Intracellular analysis indicates that TCR alpha transcription and membrane translocation of both TCR alpha and TCR beta were promoted in these conditions. Analysis of intracellular signals transduced during T-ALL differentiation indicated that CD2-ligation induced Ca2+ influx and that the ligation of CD2 and IL-2R induced distinct tyrosine phosphorylation patterns. The addition of inhibitors of tyrosine phosphorylation abolished T-ALL cell differentiation, which suggests the involvement of tyrosine kinases in this phenomenon. Together, we showed the constant maturation of leukemic early T cells after stimulation of surface CD2 and the high- affinity IL-2R.


2020 ◽  
Vol 118 (3) ◽  
pp. 353a
Author(s):  
Yannick Hamon ◽  
Anne-Marie Sartre ◽  
Anthony Formisano ◽  
Sébastien Mailfert ◽  
Didier Marguet ◽  
...  

1973 ◽  
Vol 138 (5) ◽  
pp. 1044-1055 ◽  
Author(s):  
F. Loor ◽  
B. Kindred

When the thymus from an AKR mouse (TL-, θ-AKR) is grafted to a BALB/c-nu/nu mouse (TL2, θ-C3H), the grafted thymus is rapidly repopulated by host lymphocytes, i.e., lymphocytes having the TL2 and θ-C3H T-lymphocyte membrane antigen markers. θ-C3H lymphocytes also appear rapidly in the spleen and lymph nodes. After a few weeks, BALB/c nude mice grafted with AKR thymus and normal BALB/c mice could not be distinguished on the basis of the number of TL-positive thymocytes or θ-C3H-positive lymphocytes in thymus, spleen, or lymph nodes. These experiments give a definitive proof of the existence of precursor cells for the T compartment of the lymphoid system in the nude mouse. They strongly suggest the involvement of host-derived T cells in the recovery of some T-cell functions by nude mice grafted with allogeneic thymuses.


1996 ◽  
Vol 184 (1) ◽  
pp. 149-157 ◽  
Author(s):  
C Reis e Sousa ◽  
E H Levine ◽  
R N Germain

Structural variants of an agonist peptide-major histocompatibility complex (MHC) molecule ligand can show partial agonist and/or antagonist properties. A number of such altered ligands appear to act as pure antagonists. They lack any detectable ability to induce T cell effector function and have been described as unable to induce calcium transients and turnover of inositol phosphates. This has been interpreted as an inability of these ligands to initiate any T cell receptor (TCR)-dependent signal transduction, with their antagonist properties ascribed to competition with offered agonist for TCR occupancy. Yet antagonists for mature CD8+ T cells can induce positive selection of thymocytes, implying active induction of T cell differentiation events, and partial agonists or agonist/antagonist combinations elicit a distinctive pattern of early TCR-associated tyrosine phosphorylation events in CD4+ T cells. We have therefore directly examined proximal TCR signaling in a CD8+ T cell line in response to various related ligands. TCR engagement with natural peptide-MHC class I agonist resulted in the same pattern of early TCR-associated tyrosine phosphorylation events as seen with CD4+ cells, including accumulation of both the p21 and p23 forms of phosphorylated zeta, phosphorylation of CD3 epsilon, and association of phosphorylated ZAP-70 with the TCR. Two antagonists that lacked the ability to induce any detectable CTL effector response (cytolysis, esterase release, gamma interferon secretion, interleukin-2 receptor alpha upregulation) were nevertheless found to also induce TCR-dependent phosphorylation events. In these cases, there was preferential accumulation of the p21 form of phospho-zeta without net phosphorylation of CD3 epsilon, as well as the association of nonphosphorylated ZAP-70 kinase with the receptor. These data show that variant ligands induce similar TCR-dependent phosphorylation events in CD8+ T cells as first observed in CD4+ cells. More importantly, they demonstrate that some putatively pure antagonists are actually a subset of partial agonists able to induce intracellular biochemical changes through the TCR. This delivery of a partial signal by antagonists raises the possibility that antagonism in some cases may result from active interference with stimulation of effector activity by agonist in mature T cells, while the same variant signal could selectively trigger intracellular events that allow positive without negative selection in thymocytes.


1996 ◽  
Vol 271 (13) ◽  
pp. 7686-7693 ◽  
Author(s):  
Friedrich Koch-Nolte ◽  
David Petersen ◽  
Sriram Balasubramanian ◽  
Friedrich Haag ◽  
Dominik Kahlke ◽  
...  

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