Effect of transforming growth factor-β on early and late activation events in human T cells

S. S. Ahuja, F. Paliogianni, H. Yamada, J. E. Balow, D. T. Boumpas

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137 Scopus citations


Transforming growth factors-β (TGF-β) modulate immune responses by inhibiting the proliferation of normal T lymphocytes. To examine the mechanism(s) of this inhibition, we studied the effect of TGF-β1 on selected events associated with the initiation and progression of the T lymphocyte cell cycle. Human peripheral blood T cells were stimulated with anti-CD3 mAb, PHA, PMA, or ionomycin, alone or in combination. TGF-β1 (0.5 to 10 ng/ml) partially inhibited the tyrosine phosphorylation of a 100-kDa protein, but not the calcium influx when cells were stimulated via TCR. Nuclear transcription of early activation genes (c-fos, c-jun, and c-myc) as determined by nuclear run-off assays, and steady state mRNA levels and/or protein products of intermediate activation genes (IL-2, IL-2Rα, IL-2Rβ, and transferrin receptor) were not affected by TGF-β1. Total cellular RNA synthesis and cell size after T cell stimulation were also not affected by TGF-β1. However, TGF-β1 inhibited the IL-2-dependent proliferation of Con A lymphoblasts by -50%. This inhibition was associated with the down- regulation of IL-2-mediated tyrosine phosphorylation of proteins of 120, 100, 85, 75, and 50 kDa. TGF-β1 also inhibited the IL-2-dependent phosphorylation of the retinoblastoma susceptibility gene product, which plays an important role in cell cycle progression. These results suggest that TGF-β1 inhibits T cell proliferation by down-regulating predominantly IL- 2-mediated proliferative signals.

Original languageEnglish (US)
Pages (from-to)3109-3118
Number of pages10
JournalJournal of Immunology
Issue number8 I
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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