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 Action of growth hormone in vitro on the net uptake and incorporation into protein of amino acids in muscle from intact rabbits given protein-deficient diets

1976 ◽  
Vol 35 (1) ◽  
pp. 1-10 ◽  
Author(s):  
M. R. Turner ◽  
P. J. Reeds ◽  
K. A. Munday
Keyword(s):  
Amino Acids ◽  
Growth Hormone ◽  
Protein Synthesis ◽  
Amino Acid ◽  
De Novo ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Amino Acid Incorporation ◽  
Acid Incorporation

1. Net amino acid uptake, and incorporation into protein have been measured in vitro in the presence and absence of porcine growth hormone (GH) in muscle from intact rabbits fed for 5 d on low-protein (LP), protein-free (PF) or control diets.2. In muscle from control and LP animals GH had no effect on the net amino acid uptake but stimulated amino acid incorporation into protein, although this response was less in LP animals than in control animals.3. In muscle from PF animals, GH stimulated both amino acid incorporation into protein and the net amino acid uptake, a type of response which also occurs in hypophysectomized animals. The magnitude of the effect of GH on the incorporation of amino acids into protein was reduced in muscle from PF animals.4. The effect of GH on the net amino acid uptake in PF animals was completely blocked by cycloheximide; the uptake effect of GH in these animals was dependent therefore on de novo protein synthesis.5. It is proposed that in the adult the role of growth hormone in protein metabolism is to sustain cellular protein synthesis when there is a decrease in the level of substrate amino acids, similar to that which occurs during a short-term fast or when the dietary protein intake is inadequate.

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.

The uptake of amino acids by mouse cells (strain LS) during growth in batch culture and chemostat culture: the influence of cell growth rate

1967 ◽  
Vol 168 (1013) ◽  
pp. 421-438 ◽  
Keyword(s):  
Amino Acids ◽  
Growth Rate ◽  
Amino Acid ◽  
Cell Growth ◽  
Glutamic Acid ◽  
Batch Culture ◽  
Amino Acid Uptake ◽  
Essential Amino Acids ◽  
Growth Yields ◽  
Acid Uptake

The uptake of thirteen essential amino acids by mouse LS cells in suspension culture was determined by bacteriological assay methods. Chemostat continuous-flow cultures were used to determine the effect of different cell growth rates on the quantitative amino acid requirements for growth. The growth yields of the cells ( Y = g cell dry weight produced/g amino acid utilized) were calculated for each of the essential amino acids. A mixture of the non-essential amino acids, serine, alanine and glycine increased the cell yield from the essential amino acids. The growth yields from nearly all the essential amino acids in batch culture were increased when glutamic acid was substituted for the glutamine in the medium. The growth yields from the amino acids in batch culture were much less at the beginning than at the end of the culture. The highest efficiencies of conversion of amino acids to cell material were obtained by chemostat culture. When glutamic acid largely replaced the glutamine in the medium the conversion of amino acid nitrogen to cell nitrogen was 100 % efficient (that is, the theoretical yield was obtained) at the optimum growth rate (cell doubling time, 43 h). The maximum population density a given amino acid mixture will support can be calculated from the data. It is concluded that in several routinely used tissue culture media the cell growth is limited by the amino acid supply. In batch culture glutamine was wasted by (1) its spontaneous decomposition to pyrrolidone carboxylic acid and ammonia, and (2) its enzymic breakdown to glutamic acid and ammonia, but also glutamine was used less efficiently than glutamic acid. Study of the influence of cell growth rate on amino acid uptake rates per unit mass of cells indicated that a marked change in amino acid metabolism occurred at a specific growth rate of 0.4 day -1 (cell doubling time, 43 h). With decrease in specific growth rate below 0.4 day -1 there was a marked stimulation of amino acid uptake rate per cell and essential amino acids were consumed increasingly for functions other than synthesis of cell material.

scholarly journals Action of insulin and growth hormone on protein synthesis in muscle from non-hypophysectomized rabbits

1971 ◽  
Vol 125 (2) ◽  
pp. 515-520 ◽  
Author(s):  
P. J. Reeds ◽  
K. A. Munday ◽  
M. R. Turner
Keyword(s):  
Amino Acids ◽  
Growth Hormone ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Incubation Medium ◽  
Amino Acid Uptake ◽  
Diaphragm Muscle ◽  
Acid Uptake

The separate effects of insulin and growth hormone on the uptake and incorporation of five amino acids into diaphragm muscle from non-hypophysectomized rabbits has been examined. Both growth hormone and insulin, when present in the medium separately, stimulated the incorporation into protein of the amino acids, leucine, arginine, valine, lysine and histidine. Insulin also stimulated amino acid uptake, but growth hormone did not. When insulin and growth hormone were present in the incubation medium together, the uptake and incorporation of valine, the only amino acid studied under these conditions, tended to be greater than the sum of the separate effects of the two hormones.

Amino acid uptake regulation by cell growth in cultured hepatocytes isolated from fetal and adult rats

1992 ◽  
Vol 12 (2) ◽  
pp. 135-141 ◽  
Author(s):  
S. Leoni ◽  
S. Spagnuolo ◽  
M. Massimi ◽  
F. Terenzi ◽  
L. Conti Devirgiliis
Keyword(s):  
Amino Acid ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Cell Density ◽  
Amino Acid Uptake ◽  
Growth Stimulation ◽  
Acid Uptake ◽  
Adult Rats ◽  
Dependent Growth ◽  
Differentiation Stage

Amino acid uptake mediated by system A was studied in cultured fetal and adult hepatocytes, subjected to growth stimulation by EGF and insulin, or to growth inhibition by high cell density. The mitogenic stimulation induced a strong transport increase only in fetal cells, while the cell density-dependent growth inhibition, probably mediated by molecules present on adult hepatocyte membranes, provoked the decrease of amino acid uptake only in the adult cells. The results indicate that the different modulation of amino acid transport by cell growth is dependent on the age and the differentiation stage of hepatocytes.

Protein and energy metabolism in the pre-implantation cattle embryo

2001 ◽  
Vol 26 (2) ◽  
pp. 443-446 ◽  
Author(s):  
D.G. Morris ◽  
P. Humpherson ◽  
H.J. Leese ◽  
J.M. Sreenan
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Energy Metabolism ◽  
Metabolic Rate ◽  
Protein Content ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Glucose Utilisation ◽  
Embryonic Loss

AbstractThere is no information on the metabolism of the cattle embryo during the period from day 8 to 16 a period of greatest embryonic loss. In this study the rate of protein synthesis and phosphorylation was measured in 13 to 15 day old cattle embryos. The rate of glucose utilisation and amino acid uptake/efflux by day 14 to 16 embryos was also measured. Protein synthesis and phosphorylation activity when expressed per unit of protein decreased with increasing embryo size and age. Similarly the rate of glucose utilisation was greatest for the earlier day 14 embryos. Embryos differed in their requirement for different amino acids. The pattern of uptake/efflux was similar to that of the earlier day 7 embryo. This study suggests that the metabolic rate of cattle embryos expressed per unit of protein content tends to decrease with increasing age and size from the initial burst of activity at day 13 around the time that expansion of the embryo begins.

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