Monocyte-regulated IFN-gamma production in human T cells involves CD2 signaling
| Autor: | Ag, Wingren, Dahlenborg K, Björklund M, Hedlund G, Kalland T, Ho, Sjögren, Ljungdahl A, Olsson T, Hp, Ekre, David Sansom |
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| Rok vydání: | 1993 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte Membrane Glycoproteins Time Factors T-Lymphocytes Immunology CD2 Antigens Antigen-Presenting Cells Gene Expression CHO Cells CD58 Antigens Intercellular Adhesion Molecule-1 Lymphocyte Activation Transfection Monocytes Interferon-gamma Antigens CD Cricetinae Cell Adhesion Animals Humans Immunology and Allergy RNA Messenger Receptors Immunologic Cell Adhesion Molecules Signal Transduction |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Cooperation between monocytes and T lymphocytes is essential for several aspects of immunologic activation. We have utilized PHA and IL-2-activated human T cells to characterize the role of monocytes in the regulation of T cell-derived IFN-gamma production. The limited IFN-gamma production by isolated T cells in this culture system was increased more than 10-fold when monocytes were added. No influence of monocytes was observed on TNF production or T cell proliferation. Maximal level of IFN-gamma in the cell culture supernatants was obtained when monocytes were added within 12 h after activation of the T cells with IL-2 and PHA. Addition of monocytes 48 h after activation resulted in marginal production of IFN-gamma, suggesting that T cells are sensitive to the monocyte-related signal during a short time period after activation. Cell-to-cell contact between the T cells and accessory cells was found to be necessary for enhanced IFN-gamma production because separation of the cells with a semipermeable membrane abolished the effect. mAb blocking experiments suggested the involvement of the CD2/LFA-3 but not the LFA-1/ICAM-1 pathway in monocyte regulation of T cell synthesis of IFN-gamma. Chinese hamster ovary (CHO) cells transfected with LFA-3 (CHO-LFA-3) and HLA-DR4/LFA-3 (CHO-DR4/LFA-3) strongly enhanced T cell IFN-gamma production, whereas untransfected CHO cells, CHO cells transfected with ICAM-1 (CHO-DR4/ICAM-1), and HLA-DR4 (CHO-DR4) did not support IFN-gamma production. PCR analysis and in situ hybridization demonstrated enhanced IFN-gamma mRNA levels in T cells stimulated in the presence of CHO-DR4/LFA-3 compared with untransfected CHO cells, indicating that the CD2/LFA-3 pathway regulates IFN-gamma production at the mRNA level. CHO-LFA-3 and CHO-DR4/ICAM-1 cells mediated strong adhesion to T cells, whereas untransfected CHO cells and CHO-DR4 cells failed to mediate adhesion. This suggests that the ability of CHO-LFA-3 but not CHO-DR4/ICAM-1 cells to induce IFN-gamma production was attributed to signal transduction rather than cell adhesion only. |
| Databáze: | OpenAIRE |
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