Repertoire Requirements of CD4+ T Cells That Prevent Spontaneous Autoimmune Encephalomyelitis

• Published in: The Journal of immunology (1950) Vol. 164; no. 10; pp. 5499 - 5507
• Main Authors: Olivares-Villagomez, Danyvid, Wensky, Allen K, Wang, Yijie, Lafaille, Juan J
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.05.2000
• Subjects: Adoptive Transfer; AIDS/HIV; Animals; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - transplantation; Cells, Cultured; Encephalomyelitis, Autoimmune, Experimental - genetics; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - prevention & control; Epitopes, T-Lymphocyte - immunology; Genes, T-Cell Receptor alpha; Immunization; Lymphocyte Activation - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Myelin Basic Protein - administration & dosage; Myelin Basic Protein - immunology; Ovalbumin - administration & dosage; Ovalbumin - immunology; Receptors, Antigen, T-Cell - biosynthesis; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell, alpha-beta - biosynthesis; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - transplantation; Th1 Cells - immunology; Th1 Cells - metabolism; Th1 Cells - transplantation; Th2 Cells - immunology; Th2 Cells - metabolism; Th2 Cells - transplantation
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.10.5499

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 Valpha4 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.