Synergism between the CD3 antigen-and CD2 antigen-derived signals: Exploration at the level of induction of dna-binding proteins and characterization of the inhibitory activity of cyclosporine

P. K. Sehajpal, V. K. Sharma, E. Ingulli, K. H. Stenzel, Manikkam Suthanthiran

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22 Citations (Scopus)

Abstract

We have demonstrated earlier that the crosslinkage of the CD3/TCR complex with the CD2 antigen results in the proliferation of normal human T cells. The effect of this synergism was perceptible at the level of induction of the IL-2 gene, a process critical for T cell growth. To further understand the molecular and nuclear basis for this synergism, we have explored the induction of DNA-binding proteins in highly purified normal human T cells signaled via the CD3 and/or CD2 proteins. The effect of transmembrane signaling of T cells with ionomycin, and/or sn-1, 2 dioctanoyl glycerol, was also determined. The emergence of nuclear binding proteins was investigated using interleukin-2 sequence specific oligonucleotide probes in the electrophoretic mobility shift assay. Our studies demonstrate for the first time that CD3 antigen-derived signals and CD2 antigen-derived signals are synergistic in inducing the emergence of transcription factors that bind to the NF-AT1, AP-1, and NF-kB sites located in the promoter/enhancer region of the IL-2 gene. Moreover, cyclosporine, at concentrations readily accomplished in clinical practice, was found to inhibit the emergence of these DNA-binding proteins in normal human T cells signaled via cell surface proteins implicated in antigen-dependent T cell activation and in T cells stimulated by mobilization of cellular calcium and activation of protein kinase C.

Original languageEnglish
Pages (from-to)1118-1124
Number of pages7
JournalTransplantation
Volume55
Issue number5
Publication statusPublished - 1 Jan 1993
Externally publishedYes

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ASJC Scopus subject areas

  • Transplantation

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