Molecular regulation of the IL-2 gene: rheostatic control of the immune system.
The delivery of costimulation and the effects of the anergic state impinge on IL-2 production via different molecular mechanisms. The strongest experimental support at this stage suggests that CD28 signaling effects mRNA stability of several lymphokine genes including IL-2. While there may also be transcriptional effects of CD28 signals in human cells, controversy surrounding relevant TCR mimics must be addressed. In the case of clonal anergy, however, transcriptional non-responsiveness is evident when anergic cells are restimulated with TCR and costimulatory signals. This repression affects predominantly AP-1 activity. So far, the nature of the repression has not been identified.
Umlauf
S W
SW
Laboratory of Cellular and Molecular Immunology, National Institutes of Health, Bethesda, MD 20892.
Beverly
B
B
Kang
S M
SM
Brorson
K
K
Tran
A C
AC
Schwartz
R H
RH
D000818:Animals; D018106:CD28 Antigens / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007107:Immune System; D007376:Interleukin-2 / Q000235:genetics* / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
D018106:CD28 Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell