REGULATION OF CYTOKINE AND CHEMOKINE TRANSCRIPTION IN A HUMAN TH2 TYPE T-CELL CLONE DURING THE INDUCTION-PHASE OF ANERGY

Background Selected cytokines produced by allergen specific CD4(+) T c ells from atopic individuals contribute to both the specific and non-s pecific effector mechanisms of the allergic immune response. The chemo kine family of cytokines and tumour necrosis factor (TNF)-alpha are le ucocyte regulatory and proinflammatory molecules. The chemokines inclu de interleukin (IL)-8 and the RANTES/SIS cytokines. Objective There ha s been no systematic survey of chemokine production in T-cell subtypes . Because of their wide range of biological properties, it might be ex pected that they would be closely regulated by T cells. This paper ill ustrates 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 a nd enzyme linked immunosorbent assay (ELISA) was used to quantitate so luble product. Results mRNA expression of the chemokines (IL-8, HuMIP- 1 alpha and HuMIP-1 beta) and TNF alpha is upregulated in TH2-like clo ned house dust mite reactive human CD4(+) T cells under conditions of activation and during the induction phase of anergy. Although the deve lopment of anergy superinduces mRNA for both IL-8 and TNF alpha, prote in production is low compared with that released during activation. In contrast, RANTES, a chemoattractant for CD4(+)/CD45RO(+) memory T cel ls, eosinophils and basophils, is constitutively expressed at the RNA level by the T cells and not modulated by signals of activation and an ergy induction. The production of IL-2, IL-4 and IL-5 mRNA and protein s during the induction of anergy peaks at 2 h after stimulation, where as the kinetics following activation of the T cells is delayed in comp arison. Conclusion These data show that the induction of the anergic s tate coincides with post-transcriptional regulation of selected cytoki ne genes. Further study of these phenomena will impact on our understa nding of the mechanisms of induction of anergy and the regulation of a llergic immune responses in desensitization.