title: Monocyte-regulated IFN-gamma production in human T cells involves CD2 signaling.
abstract: 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.
authors.affiliation: Wallenberg Laboratory, Department of Tumor Immunology, University of Lund, Sweden.
authors.forename: A G
authors.initials: AG
authors.lastname: Wingren
authors.forename: K
authors.initials: K
authors.lastname: Dahlenborg
authors.forename: M
authors.initials: M
authors.lastname: Björklund
authors.forename: G
authors.initials: G
authors.lastname: Hedlund
authors.forename: T
authors.initials: T
authors.lastname: Kalland
authors.forename: H O
authors.initials: HO
authors.lastname: Sjögren
authors.forename: A
authors.initials: A
authors.lastname: Ljungdahl
authors.forename: T
authors.initials: T
authors.lastname: Olsson
authors.forename: H P
authors.initials: HP
authors.lastname: Ekre
authors.forename: D
authors.initials: D
authors.lastname: Sansom
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D018801:CD2 Antigens; D018968:CD58 Antigens; D016466:CHO Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D006224:Cricetinae; D015870:Gene Expression; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology; D009000:Monocytes / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*; D013997:Time Factors; D014162:Transfection
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma