DOI: 10.4049/jimmunol.164.10.5499. Repertoire Requirements of CD4+ T Cells That Prevent Spontaneous Autoimmune Encephalomyelitis

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

10.4049/jimmunol.164.10.5499

Crossref journal-article

Oxford University Press (OUP)

The Journal of Immunology (286)

Abstract

Abstract 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.

Bibliography

Olivares-VillagoÌmez, D., Wensky, A. K., Wang, Y., & Lafaille, J. J. (2000). Repertoire Requirements of CD4+ T Cells That Prevent Spontaneous Autoimmune Encephalomyelitis. The Journal of Immunology, 164(10), 5499â5507.

Authors 4

Danyvid Olivares-Villagómez (first)
Allen K. Wensky (additional)
Yijie Wang (additional)
Juan J. Lafaille (additional)

References 68 Referenced 76

Dates

Type	When
Created	11 years, 4 months ago (April 21, 2014, 10:30 p.m.)
Deposited	7 months, 3 weeks ago (Jan. 2, 2025, 1:37 p.m.)
Indexed	3 months, 3 weeks ago (May 2, 2025, 10:47 a.m.)
Issued	25 years, 3 months ago (May 15, 2000)
Published	25 years, 3 months ago (May 15, 2000)
Published Print	25 years, 3 months ago (May 15, 2000)

Funders 0

None

BibTeX

@article{Olivares_Villago_mez_2000, title={Repertoire Requirements of CD4+ T Cells That Prevent Spontaneous Autoimmune Encephalomyelitis}, volume={164}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.164.10.5499}, DOI={10.4049/jimmunol.164.10.5499}, number={10}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Olivares-Villagómez, Danyvid and Wensky, Allen K. and Wang, Yijie and Lafaille, Juan J.}, year={2000}, month=may, pages={5499–5507} }

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