Transforming growth factor-β1 induces antigen-specific unresponsiveness in naive t cells
| Autor: | William O. Weigle, Thuy Pham, Marilyn L. Thoman, Kathleen M. Gilbert, Kimberley Bauche |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Mice Inbred A medicine.drug_class medicine.medical_treatment Immunology Receptors Antigen T-Cell Mice Transgenic Biology Lymphocyte Activation Monoclonal antibody Mice Antigen Antigens CD Transforming Growth Factor beta Immune Tolerance medicine Animals Antigens Cells Cultured CD86 MHC class II Membrane Glycoproteins T-cell receptor Histocompatibility Antigens Class II General Medicine Transforming growth factor beta Cell biology Cytokine B7-1 Antigen biology.protein Interleukin-2 B7-2 Antigen Immunosuppressive Agents CD80 |
| Zdroj: | Immunological Investigations. 26:459-472 |
| ISSN: | 1532-4311 0882-0139 |
| Popis: | Transforming growth factor-beta 1 (TGF-beta 1) is a cytokine with complex immunomodulatory effects including the ability to inhibit the onset or severity of autoimmune disease. This study was designed to test the possibility that one mechanism by which TGF-beta 1 exerts its immunosuppressive effects is by inducing antigen (Ag)-specific unresponsiveness in CD4+ cells. TGF-beta 1 was shown here to inhibit the Ag-specific proliferation of naive CD4+ cells from T cell receptor (TCR) transgenic mice. More importantly, the naive CD4+ cells exposed to TGF-beta 1 and Ag, but not to TGF-beta 1 alone, in primary cultures were unable to proliferate or secrete IL-2 in response to a subsequent Ag challenge following removal of TGF-beta 1 from the cultures. Anti-CD28 mAb partially blocked the Ag-specific inactivation induced by TGF-beta 1 in naive CD4+ cells. The inhibitory effects of TGF-beta 1 on CD4+ cells are not mediated by alterations in APC costimulation since TGF-beta 1 did not inhibit the Ag-induced expression of MHC class II molecules, CD80 or CD86 on splenic APC. Taken together, the results suggest that the immunosuppressive activities of TGF-beta 1 encompass direct induction of Ag-specific unresponsiveness in naive CD4+ cells. |
| Databáze: | OpenAIRE |
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