Constitutive expression c-fos, c-jun, and NF kappa B mRNA is in nucleated fetal blood cells and up-regulation of c-fos and c-jun with anti-CD3 stimulation.
Fetal and neonatal lymphocytes are relatively resistant to activation and cytokine production when stimulated either via their T-cell antigen receptors or lectins. The molecular mechanism(s) responsible for this phenomenon have not been clearly elucidated. We have hypothesized that such defects in fetal/neonatal T-cell activation may be due to lack of expression of the transcriptional regulatory elements required for T-cell activation. We used reverse transcriptase-polymerase chain reaction to examine both fetal and term neonatal cord bloods for mRNA expression of three transcription factors implicated in T-cell activation: c-jun, c-fos, and NF kappa B (p50 subunit). We demonstrate that mRNAs for all three of these regulatory factors are expressed in fetal blood cells by the 27th week of gestation and in term cord bloods. Activation of term infant cord blood mononuclear cells with anti-CD3 monoclonal antibodies resulted in up-regulation of both c-jun and c-fos mRNAs within 15 min of stimulation. However, secretion of IL-2 by anti-CD3-stimulated cord blood mononuclear cells was still blunted compared with control cells from adults. We conclude that fetal nucleated blood cells constitutively express important genes for cytokine regulation and are able to increase intracellular accumulation of the mRNAs for these factors in response to anti-CD3 stimulation. Thus, qualitative differences in the capacity to regulate these factors could not be shown in fetal blood cells. Quantitative experiments comparing binding of these transcription factors to the IL-2 promoter are currently under investigation.
Jarvis
J N
JN
Division of Immunology/Rheumatology, Wayne State University School of Medicine, Detroit, Mich., USA. james-jarvis@ouhsc.edu
Zhao
L
L
Xu
C S
CS
Moore
H T
HT
Berry
S
S
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000737:chemistry* / Q000166:cytology; D016762:Genes, fos / Q000235:genetics / Q000502:physiology; D016758:Genes, jun / Q000235:genetics / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011519:Proto-Oncogenes / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D013950:Thymus Gland / Q000378:metabolism; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007376:Interleukin-2; D016328:NF-kappa B; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma