Repertoire requirements of CD4+ T cells that prevent spontaneous autoimmune encephalomyelitis
| Autor: | Allen K. Wensky, Juan J. Lafaille, Danyvid Olivares-Villagómez, Yijie Wang |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
CD4-Positive T-Lymphocytes
Encephalomyelitis Autoimmune Experimental Ovalbumin Receptors Antigen T-Cell alpha-beta Immunology Population Receptors Antigen T-Cell Epitopes T-Lymphocyte chemical and pharmacologic phenomena Mice Transgenic Streptamer Biology Lymphocyte Activation Myelin Interleukin 21 Mice Th2 Cells T-Lymphocyte Subsets medicine Immunology and Allergy Cytotoxic T cell Animals IL-2 receptor education Cells Cultured Mice Knockout education.field_of_study Experimental autoimmune encephalomyelitis T-cell receptor Myelin Basic Protein Th1 Cells medicine.disease Adoptive Transfer Cell biology Mice Inbred C57BL medicine.anatomical_structure Immunization Genes T-Cell Receptor alpha |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 164(10) |
| ISSN: | 0022-1767 |
| Popis: | Spontaneous experimental autoimmune encephalomyelitis arises in 100% of mice exclusively harboring myelin basic protein-specific T cells, and can be prevented by a single injection of CD4+ T cells obtained from normal donors. Given the powerful regulatory effect of the transferred T cells, we further investigated their properties, and, in particular, their repertoire requirements. Transfer of monoclonal OVA-specific CD4+ T cells did not confer protection from disease even when present at very high proportions (about 80% of total lymphocytes). Lack of protection was also evident after immunization of these animals with OVA, indicating that not just any postthymic CD4+ T cells has the potential to become regulatory. However, protection was conferred by cells bearing limited TCR diversity, including cells expressing a single Vα4 TCR chain or cells lacking N nucleotides. We also investigated whether coexpression of the myelin basic protein-specific TCR with another TCR in a single cell would alter either pathogenesis or regulation. This was not the case, as myelin basic protein-specific/OVA-specific recombinase activating gene-1−/− double TCR transgenic mice still developed experimental autoimmune encephalomyelitis spontaneously even after immunization with OVA. Based on this evidence, we conclude that CD4+ T regulatory cells do not express canonical TCRs and that the altered signaling properties brought about by coexpression of two TCRs are not sufficient for the generation of regulatory T cells. Instead, our results indicate that regulatory T cells belong to a population displaying wide TCR diversity, but in which TCR specificity is central to their protective function. |
| Databáze: | OpenAIRE |
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