Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway.
Quiescent T cells can be induced to express many genes by mitogen or antigen stimulation. The messenger RNAs of some of these genes undergo relatively rapid degradation compared to messenger RNAs from constitutively expressed genes. A T cell activation pathway that specifically regulates the stability of messenger RNAs for the lymphokines interleukin-2, interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor is induced by stimulation of the CD28 surface molecule. This pathway does not directly affect the steady-state messenger RNA level, transcription, or messenger RNA half-life of other T cell activation genes, including c-myc, c-fos, IL-2 receptor, and the 4F2HC surface antigen. These data show that stimuli received at the cell surface can alter gene expression by inducing specific changes in messenger RNA degradation.
Lindstein
T
T
Howard Hughes Medical Institute, University of Michigan, Ann Arbor 48109.
June
C H
CH
Ledbetter
J A
JA
Stella
G
G
Thompson
C B
CB
D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018106:CD28 Antigens; D017252:CD3 Complex; D003115:Colony-Stimulating Factors / Q000235:genetics; D004355:Drug Stability; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007376:Interleukin-2; D008222:Lymphokines; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor