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B in FGF Receptor-Bearing Jurkat T Cells1
Departments of Medicine and Microbiology/Immunology and Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville, TN 37232
Fibroblast growth factors (FGFs) are heparin-binding proteins
crucial to embryogenesis, angiogenesis, and wound healing. FGF-1 is
abundantly expressed in the synovium in rheumatoid arthritis and in
rejecting allografts, sites of chronic immune-mediated inflammation.
The frequency of FGF-1-responsive T cells is increased in the
peripheral blood of these disorders, and a high percentage of
infiltrating T cells in rheumatoid arthritis synovium express receptors
for FGF-1. To understand the action of FGF-1 in T cells, studies were
initiated in Jurkat T cells that express the signaling isoform of FGF
receptor-1. These experiments show that FGF-1 stimulation of Jurkat T
cells provides a second signal that augments TCR-mediated IL-2
production. Analogous to costimulation via CD28, this activity is
mediated through activation of Rel/
B, a family of transcription
factors known to regulate IL-2 and other activation-inducible proteins.
FGF-1 alone induces modest nuclear translocation of B-binding
proteins, and this translocation is enhanced by the combination of
anti-CD3 and FGF-1. This NF-B binding complex is composed of
transcriptionally active p65(RelA)/p50 heterodimers and results
primarily from the targeted degradation of IB-
, an inhibitor that
sequesters Rel/B in the cytoplasm. These data are the first to show
a connection between FGF-1 signaling and NF-B activation outside of
embryonic development. The signaling events that link FGF receptor-1
engagement and NF-B activation in Jurkat are probably distinct from
the CD28 costimulation pathway, since FGF-1-induced Rel/B binding
proteins do not contain significant levels of c-Rel and are not
identical with the CD28 response complex.
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