Regulation of cytokine and chemokine transcription in a human TH2 type T-cell clone during the induction phase of anergy

R. E. O'Hehir, R. A. Lake, T. J. Schall, H. Yssel, E. Panagiotopoulou, J. R. Lamb

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16 Citations (Scopus)

Abstract

Background. Selected cytokines produced by allergen specific CD4+ T cells from atopic individuals contribute to both the specific and non-specific effector mechanisms of the allergic immune response. The chemokine family of cytokines and tumour necrosis factor (TNF)-α are leucocyte regulatory and proinflammatory molecules. The chemokines include interleukin (IL)-8 and the RANTES/SIS cytokines. Objective. There has been no systematic survey of chemokine production in T-cell subtypes. Because of their wide range of biological properties, it might be expected that they would be closely regulated by T cells. This paper illustrates one way (through the characterization of T-cell clones) these questions might be addressed. Methods. Northern blot analysis was used to quantitate steady state transcription of selected cytokine genes and enzyme linked immunosorbent assay (ELISA) was used to quantitate soluble product. Results. mRNA expression of the chemokines (IL-8, HuMIP-1α and HuMIP-1β) and TNFα is upregulated in TH2-like cloned house dust mite reactive human CD4+ T cells under conditions of activation and during the induction phase of anergy. Although the development of anergy superinduces mRNA for both IL-8 and TNFα, protein production is low compared with that released during activation. In contrast, RANTES, a chemoattractant for CD4+/CD45RO+ memory T cells, eosinophils and basophils, is constitutively expressed at the RNA level by the T cells and not modulated by signals of activation and anergy induction. The production of IL-2, IL-4 and IL-5 mRNA and proteins during the induction of anergy peaks at 2h after stimulation, whereas the kinetics following activation of the T cells is delayed in comparison. Conclusion. These data show that the induction of the anergic state coincides with post-transcriptional regulation of selected cytokine genes. Further study of these phenomena will impact on our understanding of the mechanisms of induction of anergy and the regulation of allergic immune responses in desensitization.

Original languageEnglish
Pages (from-to)20-27
Number of pages8
JournalClinical & Experimental Allergy
Volume26
Issue number1
DOIs
Publication statusPublished - 30 Jan 1996
Externally publishedYes

Keywords

  • Cytokines
  • House dust mite
  • Immunoregulation
  • T cells
  • Tolerance

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