DIRECT-CONTACT BETWEEN T-LYMPHOCYTES AND HUMAN DERMAL FIBROBLASTS OR SYNOVIOCYTES DOWN-REGULATES TYPE-I AND TYPE-III COLLAGEN PRODUCTION VIA CELL-ASSOCIATED CYTOKINES

In many inflammatory diseases where tissue remodeling occurs, T cells are in close contact with mesenchymal cells. We investigated the effec t of direct cell-cell contact between peripheral blood T lymphocytes o r HUT-78 lymphoma cells and dermal fibroblasts or synoviocytes on the deposition of the major extracellular matrix components: types I and I II collagen. Incubation of dermal fibroblasts and synoviocytes with pl asma membrane preparations from resting T cells slightly increased the production of collagen I but did not significantly affect that of col lagen III. Conversely, direct contact with either plasma membranes or fixed phytohemagglutinin/phorbol myristate acetate activated T cells m arkedly inhibited the synthesis of types I and III collagen by 60-70% in untreated dermal fibroblasts and synoviocytes and by 85% in transfo rming growth factor beta-stimulated fibroblasts. This decrease of coll agen synthesis was abrogated when fixed T cells were separated physica lly hom fibroblasts, demonstrating that direct contact between the two cell types was necessary. This inhibition was associated with a marke d decrease in steady-state levels of pro-alpha 1(I) and pro-alpha 1(II I) collagen mRNAs. T cell contact decreased the transcription rate but did not significantly alter the stability of the alpha 1(I) and alpha 1(III) transcripts. Finally, using neutralizing antibodies or cytokin e inhibitors we provide evidence that this inhibition of extracellular matrix production mediated by T cell contact was partially due to add itive effects of T cell membrane-associated interferon gamma, tumor ne crosis factor alpha, and interleukin-1 alpha.