Self-reactive T cells are present in the peripheral lymphoid tissues of cyclosporin A-treated mice.

Abstract:

:Cyclosporin A (CsA) prevents most immature thymocytes from progressing to a mature phenotype and blocks the deletion of T cells that express self-specific TCR in the small population of cells that achieve maturity. The latter effect may explain the paradoxical observation that this immunosuppressive drug can induce autoimmunity in irradiated rodents and humans if administered while new T cells are developing in the thymus. This study shows that the repopulation of the periphery with mature T cells is delayed in irradiated CsA-treated mice, presumably because CsA blocks T cell development in the thymus. The peripheral repertoire of these mice contained self-reactive IL-2 producing T cells that could be detected in a sensitive limiting dilution assay. In addition, self-reactive T cell hybridomas were isolated from the IL-2 receptor+ population present in CsA-treated mice. One of these hybridomas expressed a TCR V beta chain that is normally expressed on thymocytes that are deleted via recognition of self-antigens. Despite the presence of self-reactive T cells that had escaped clonal deletion, CsA-treated mice rarely developed lethal autoimmune disease, implying that a peripheral mechanism of tolerance can prevent the onset of autoimmune disease.

journal_name

Int Immunol

journal_title

International immunology

authors

Urdahl KB,Pardoll DM,Jenkins MK

doi

10.1093/intimm/4.12.1341

subject

Has Abstract

pub_date

1992-12-01 00:00:00

pages

1341-9

issue

12

eissn

0953-8178

issn

1460-2377

journal_volume

4

pub_type

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