Distinct costimulation dependent and independent autoreactive T-cell clones in primary biliary cirrhosis
| Autor: | Yasuni Nakanuma, Koichi Tsuneyama, Takashi Kamihira, Mine Harada, Hiromi Ishibashi, M. Eric Gershwin, Kenichi Harada, Eishi Baba, Shinji Shimoda, Minoru Nakamura, Mizuki Handa, Akira Kawano |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cytotoxicity Immunologic T-Lymphocytes T cell Antigen-Presenting Cells Autoimmunity Pyruvate Dehydrogenase Complex Biology Dihydrolipoyllysine-Residue Acetyltransferase medicine.disease_cause medicine Humans Antigen-presenting cell Cells Cultured Clonal Anergy Hepatology Clonal anergy Liver Cirrhosis Biliary T-cell receptor Gastroenterology CD28 Peripheral tolerance hemic and immune systems Coculture Techniques Peptide Fragments Clone Cells medicine.anatomical_structure Immunology Bile Ducts Clone (B-cell biology) Cell Division |
| Zdroj: | Gastroenterology. 125:1379-1387 |
| ISSN: | 0016-5085 |
| DOI: | 10.1016/j.gastro.2003.07.013 |
| Popis: | Background & Aims: Previous work has suggested that CD4 + CD28 − or costimulation-independent T cells are increased in autoimmune diseases. In this study, we compared frequency and qualitative characteristics of autoreactive costimulation-independent or CD4 + CD28 − T cells in primary biliary cirrhosis (PBC) by taking advantage of the well-defined immunodominant autoepitope of the E2 component of pyruvate dehydrogenase (PDC-E2). Methods: We determined the frequency of costimulation-independent autoreactive T cells that respond to PDC-E2 163–176 and the frequency of CD4 + CD28 − T cells. Finally, we determined the role of biliary epithelial cells (BEC) as both an antigen-presenting cell or, alternatively, as a target cell for T-cell-mediated cytotoxicity. Results: The precursor frequency of costimulation-independent CD4 + T cells that respond to PDC-E2 163–176 and the frequency of CD4 + CD28 − T cells were dramatically elevated in PBC. Furthermore, 2 types of T-cell clones that respond to PDC-E2 163–176 emerged from this study. One type was costimulation dependent and the other costimulation independent. Both types of clones lyse BEC in a similar effector target (E/T) ratio distribution. However, BEC did not help the proliferation of any T-cell clones. Furthermore, costimulation-independent T-cell clones do not become anergic by BEC. Conclusions: In PBC, costimulation-independent autoreactive T cells, which do not become anergic, increase and maintain the autoimmune response. In controls, although autoantigens are expressed on BEC and autoantigen-reactive T cells exist around BEC, autoantigen-reactive T cells are costimulation dependent and will become anergic and maintain peripheral tolerance. |
| Databáze: | OpenAIRE |
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