Differential regulation of transforming growth factor β and interleukin 2 genes in human T cells: Demonstration by usage of novel competitor DNA constructs in the quantitative polymerase chain reaction

B. Li, P. K. Sehajpal, A. Khanna, H. Vlassara, A. Cerami, K. H. Stenzel, M. Suthanthiran

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Abstract

The regulation of mKNA encoding transforming growth factor β (TGF-β) and interleukin 2 (IL,2) in normal human T cells was explored using novel competitor DNA constructs in the quantitative polymerase chain reaction and accessory cell-independent T cell activation models. Our experimental design revealed the following: (a) TGF-β mRNA and IL-2 mRNA are regulated differentially in normal human T cells, quiescent or signaled with the synergistic combinations of: sn-l,2-dioctanoylglycerol and ionomycin or anti-CD3 monoclonal antibody (mAb) and anti- CD2 mAb; (b) the steady-state level of TGF-β mRNA in the stimulated T cells, in contrast to that of II.2 mRNA, is increased by the immunosuppressant cyclosporine (CsA); and (c) the paradoxical effect of CsA on TGF-β mRNA levels is also appreciable at the level of production of functionally active TGF-β protein. Our findings, in addition to demonstrating the utility of the competitor DNA constructs for the precise quantification of immunoregulatory cytokines, suggest a novel and unifying mechanistic basis for the immunosuppression and some of the complications (e.g., renal fibrosis) associated with CsA usage.

Original languageEnglish
Pages (from-to)1259-1262
Number of pages4
JournalJournal of Experimental Medicine
Volume174
Issue number5
DOIs
Publication statusPublished - 1 Nov 1991

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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