Induction of Tolerance in CD8+ T Cells to a Transgenic Autoantigen Expressed in the Liver Does Not Require Cross-Presentation
| Autor: | Philip D. Greenberg, Ryan M. Teague, Junko Morimoto, Claes Öhlén, Xiaoxio Tan |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Adoptive cell transfer
Immunology Epitopes T-Lymphocyte Gene Products gag Mice Transgenic CD8-Positive T-Lymphocytes Major histocompatibility complex Autoantigens Resting Phase Cell Cycle Lymphocyte Depletion Mice Interleukin 21 Cross-Priming Cell Line Tumor Animals Immunology and Allergy Cytotoxic T cell IL-2 receptor Antigen-presenting cell Cells Cultured Serum Albumin Mice Inbred BALB C biology Cross-presentation Friend murine leukemia virus Cell biology Mice Inbred C57BL Self Tolerance Liver biology.protein CD8 |
| Zdroj: | The Journal of Immunology. 178:6849-6860 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.178.11.6849 |
| Popis: | Cross-presentation of normal self and candidate tumor Ags by bone marrow (BM)-derived APCs that have not been activated has been demonstrated as a major mechanism contributing to acquisition of tolerance by mature T cells that first encounter an Ag in the periphery (cross-tolerance). Following adoptive transfer of naive TCR-transgenic CD8+ T cells into a host expressing a transgenic Ag that is a potentially targetable tumor Ag in normal hepatocytes as a self-Ag, we found that the majority of Ag-specific CD8+ T cells were deleted, with the remaining cells rendered anergic. Studies in BM chimeric mice and with purified cell populations demonstrated that these events were not dependent on cross-presentation by BM-derived APCs including Kupffer cells or liver sinusoidal endothelial cells, and apparently can occur entirely as a consequence of direct recognition of Ag endogenously processed and presented by hepatocytes. Direct recognition of Ag-expressing hepatocytes in vivo induced a proliferative response and up-regulation of activation markers in responding CD8+ T cells, but proliferating cells did not accumulate, with most cells rapidly eliminated, and the persisting T cells lost the capacity to proliferate in response to repeated Ag stimulation. The results suggest that parenchymal tissues may retain the capacity to directly regulate in vivo responses to self-Ags processed and presented in the context of class I MHC molecules. |
| Databáze: | OpenAIRE |
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