geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T-bet and Eomesodermin


, : The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T-bet and Eomesodermin. Immunity 32(1): 67-78

The mechanisms underpinning integration of instructions that program naive CD8+ T cells for effector and/or memory differentiation are not well understood. Herein, we demonstrate that interleukin-12 (IL-12) enhanced and sustained antigen and costimulatory molecule (B7.1)-induced mTOR kinase activity in naive CD8+ (OT-I) T cells via phosphoinositide 3-kinase and STAT4 transcription factor pathways. Blocking mTOR activity by rapamycin reversed IL-12-induced effector functions because of loss of persistent expression of the transcription factor T-bet. Rapamycin treatment of IL-12-conditioned OT-I cells promoted persistent Eomesodermin expression and produced memory cell precursors that demonstrated enhanced sustenance and antigen-recall responses upon adoptive transfer. The memory cell precursors showed greater tumor efficacy than IL-12-conditioned effector OT-I cells. These results identify mTOR as the central regulator of transcriptional programs that determine effector and/or memory cell fates in CD8+ T cells. Targeting mTOR activity offers new opportunities to regulate CD8+ T cell-mediated immunity.

US$19.90

PMID: 20060330

DOI: 10.1016/j.immuni.2009.10.010


Other references

Usansky, J.; Sirossian, S.; Nguyen, T.; Shackleton, M.; Zolezio, H.; Tang Liu, D., 1997: The effect of a multiple dosing regimen on the absorption, disposition and melanin binding of 3H-polyhexamethylene biguanide. Investigative Ophthalmology & Visual Science 38(4 PART 1-2): S1108

Jana, S.N.; Garg, S.K.; Thirunavukkarasu, A.R.; Anita Bhatnagar; Alok Kalla; Patra, B.C., 2006: Use of additional substrate to enhance growth performance of milkfish, Chanos chanos (Forsskal) in inland saline groundwater ponds. Milkfish, Chanos chanos, fingerlings were cultured in inland saline groundwater ponds. Bamboo poles as additional substrate were used to increase the surface area of the ponds (Treated ponds). Controls, without the provision of additional substrat...

Jahn, G., 1991: Temperate deciduous forests of Europe. Ecosystems of the world: ) 372-502

Ratnasinghe, G.; Hague, N.G.M., 1997: Efficacy of entomopathogenic nematodes against the diamondback moth Plutella xylostella (Lepidoptera: Yponomeutidae). The efficacy of Steinernema carpocapsae, S. riobravis [S. riobravae] and S. feltiae was evaluated in laboratory tests against different stages in the life cycle of P. xylostella. Against insect larvae, the LT50 was less than 3 h for all 3 nematode...

Williamson, J.R.; Corbett, J.A.; Mcdaniel, M.L.; Tilton, R.G., 1998: Method of inhibiting nitric oxide formation. Official Gazette of the United States Patent & Trademark Office Patents 1216(3): 2966, Nov 17

Anonymous, 1978: Normansfield Hospital inquiry. British Medical Journal 2(6153): 1709-1709

Butterworth, E.J.; Walsh, E.G.; Hugg, J.W., 2001: A TiO(2) dielectric filled toroidal radio frequency cavity resonator for high-field NMR. R(F) performance in high-field MRI applications is improved by filling the resonator with material of relative dielectric constant approximating that of human soft tissue. We demonstrate this by filling a toroidal cavity resonator operating in TEM...

Kanematsu, T.; Higashi, H.; Takenaka, K.; Matsumata, T.; Maehara, Y.; Sugimachi, K., 1990: Bioenergy status of human liver during and after warm ischemia. Changes in the human liver's cellular bio-energy status during warm ischaemia and the subsequent blood reflow period were investigated by means of adenosine triphosphate (ATP) assay. In 8 patients, the average level of ATP in the liver tissue...

Khairat, O., 1966: An efficient general-purpose culture medium for aerobes and anaerobes. Thirty-three microbial strains (all but one freshly isolated from human pathogoglic material) and comprising aerobes, anaerobes, and CO2-dependent bacteria, were used to compare the growth capabilities of a new general-purpose medium, with two com...

Clausell, N.; Silver, M.D.; Daly, P.A., 1995: Atheroembolism in an endomyocardial biopsy from a cardiac transplant recipient after coronary angioplasty. A case of a coronary atheroembolism after coronary angioplasty was detected by routine myocardial biopsy six years after cardiac transplant. The patient had had three balloon angioplasties within a five week interval for symptomatic accelerated co...