CD40 ligation in the presence of self-reactive CD8 T cells leads to severe immunopathology
| Autor: | Hanspeter Pircher, Evelyn Roth, Johannes Schwartzkopff |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
Adoptive cell transfer T cell Receptors Antigen T-Cell alpha-beta Immunology Antigen-Presenting Cells Mice Transgenic CD8-Positive T-Lymphocytes Lymphocyte Activation Autoantigens Epitope Mice CD28 Antigens Lymphopenia medicine Immune Tolerance Immunology and Allergy Cytotoxic T cell Animals CD40 Antigens B cell Peripheral tolerance induction B-Lymphocytes CD40 biology CD28 Antibodies Monoclonal Mice Inbred C57BL medicine.anatomical_structure Injections Intravenous biology.protein B7-1 Antigen Female Spleen Bacterial Outer Membrane Proteins |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 168(10) |
| ISSN: | 0022-1767 |
| Popis: | Previous work has shown that stimulation of APCs via CD40 strongly influences the outcome of a CD8 T cell response. In this study, we examined the effect of CD40 ligation on peripheral tolerance induction of self-reactive CD8 T cells in an adoptive transfer model. Naive CD8 T cells from TCR-transgenic (tg) mice specific for the gp33 epitope of lymphocytic choriomeningitis virus were tolerized when transferred into H8-tg mice expressing the gp33 epitope under the control of a MHC class I promoter. However, if the H8 recipient mice were treated with agonistic anti-CD40 Abs, TCR-tg cells vigorously proliferated, and induced destruction of lymphoid organs and hepatitis. Break of peripheral tolerance induction was B cell independent and did not require CD28/B7 interactions. These findings provide further in vivo evidence for the crucial role of the activation state of the APC in peripheral tolerance induction and suggest the need for caution in systemically activating APC via CD40 ligation in the presence of self-reactive T cells. |
| Databáze: | OpenAIRE |
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