ABSTRACT
CD8+ T cells often differentiate into highly cytotoxic cells, secreting a Th1-like or type 1 cytokine pattern characterized by the production of IFN-gamma. However, cytotoxic, and in some reports, noncytotoxic, type 2 cells that secrete IL-4, IL-5, or IL-10 instead of IFN-gamma, can be generated when CD8+ T cells are primed in the presence of IL-4. Here, we show that IL-4 can also generate typical CD8 type 1 responses. Indeed, while presence of TGF-beta biases the development of CD8 T cells that, then, produce little cytolytic activity and IFN-gamma, addition of IL-4 results in the recovery of cytotoxicity and IFN-gamma production. The cooperative effects of TGF-beta and IL-4 imply dual functions, not only for IL-4, but also for TGF-beta. Indeed, depending on the presence or absence of IL-4, TGF-beta either inhibits or induces the generation of type 1 CD8+ T cells. Physiologically, the ratio of local IL-4/TGF-beta concentration may therefore be a critical element in determining the outcome of T cell responses to pathogen and autoantigens. It allows CD8 T cells to switch from an immunotolerant state in the presence of only TGF-beta or IL-4, to an immunocompetent proinflammatory type 1 state in the absence or presence of both cytokines.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Interleukin-4/physiology , Lymphocyte Activation/immunology , T-Lymphocyte Subsets/immunology , Transforming Growth Factor beta/physiology , Animals , CD8 Antigens/biosynthesis , CD8-Positive T-Lymphocytes/metabolism , Cells, Cultured , Cytotoxicity, Immunologic , Down-Regulation/immunology , Drug Synergism , Immunosuppressive Agents/pharmacology , Interleukin-4/antagonists & inhibitors , Mice , STAT6 Transcription Factor , Signal Transduction/immunology , T-Lymphocyte Subsets/metabolism , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Regulatory/immunology , Trans-Activators/metabolismABSTRACT
CD8+ T cells are a major defense against viral infections and intracellular parasites. Their production of interferon-gamma (IFN-gamma) and their cytolytic activity are key elements in the immune response to these pathogens. Mature mouse CD8+ T cells that were activated in the presence of interleukin-4 (IL-4) developed into a CD8-CD4- population that was not cytolytic and did not produce IFN-gamma. However, these CD8- cells produced large amounts of IL-4, IL-5, and IL-10 and helped activate resting B cells. Thus, CD8 effector functions are potentially diverse and could be exploited by infectious agents that switch off host protective cytolytic responses.
Subject(s)
B-Lymphocytes/immunology , CD8 Antigens/analysis , Interleukins/biosynthesis , Lymphocyte Activation , T-Lymphocyte Subsets/immunology , Animals , CD4 Antigens/analysis , Cell Line , Cells, Cultured , Cytotoxicity, Immunologic , Immunophenotyping , Interleukin-10/biosynthesis , Interleukin-2/pharmacology , Interleukin-4/biosynthesis , Interleukin-4/pharmacology , Interleukin-5/biosynthesis , Ionomycin/pharmacology , Membrane Glycoproteins/genetics , Mice , Perforin , Pore Forming Cytotoxic Proteins , T-Lymphocytes, Cytotoxic/immunology , Tetradecanoylphorbol Acetate/pharmacologyABSTRACT
PIP: The authors analyze the migration of ethnic Germans from Eastern Europe and the former Soviet Union to West Germany during the 1980s. They note that many of the problems associated with the absorption of these migrants stem from their uneven geographical distribution and concentration in certain Lander such as North Rhine-Westphalia. Measures taken by the German government in the areas of employment and housing to relieve these problems are described.^ieng
Subject(s)
Acculturation , Demography , Emigration and Immigration , Employment , Housing , Public Policy , Developed Countries , Economics , Europe , Geography , Germany, West , Population , Population Dynamics , Residence Characteristics , Social ChangeABSTRACT
Kupffer cells isolated from the liver of normal rats were checked for their antiviral activities. The intrinsic antiviral effect against vaccinia virus was high whether the cells were activated in vitro with endotoxin or not. The expression of the extrinsic antiviral activity measured by mixing isolated Kupffer cells with vaccinia-virus-infected target cells was remarkably enhanced by prior treatment of the Kupffer cells with LPS. Interferon was shown to be not responsible for that inhibitory activity. Different experimental data suggest that the virus replication in the target cells is blocked at a late stage in the replication cycle.
Subject(s)
Kupffer Cells/immunology , Viral Interference , Animals , Cells, Cultured , Endotoxins/pharmacology , Macrophage Activation , Macrophages/immunology , Male , Mice , Mice, Inbred C3H , Rats , Rats, Inbred Strains , Vaccinia virus/growth & development , Virus ReplicationABSTRACT
Kupffer cells from the liver of normal rats were checked for their natural cytostatic capabilities using an in vitro target cell growth inhibition assay. A strong cytostatic effect was observed on an human tumor cell line and was shown to be exerted on various transformed or normal target cells with only small differences in their susceptibility. The inhibition of target cell proliferation was shown to depend on the effector/target cell ratio. Different experimental data suggest that an intimate membranal contact between Kupffer cells and target cells is required.
