IL-10-producing CD4+CD25+ regulatory T cells play a critical role in granulocyte-macrophage colony-stimulating factor-induced suppression of experimental autoimmune thyroiditis.
Our earlier study showed that GM-CSF has the potential not only to prevent, but also to suppress, experimental autoimmune thyroiditis (EAT). GM-CSF-induced EAT suppression in mice was accompanied by an increase in the frequency of CD4(+)CD25(+) regulatory T cells that could suppress mouse thyroglobulin (mTg)-specific T cell responses in vitro, but the underlying mechanism of this suppression was not elucidated. In this study we show that GM-CSF can induce dendritic cells (DCs) with a semimature phenotype, an important characteristic of DCs, which are known to play a critical role in the induction and maintenance of regulatory T cells. Adoptive transfer of CD4(+)CD25(+) T cells from GM-CSF-treated and mTg-primed donors into untreated, but mTg-primed, recipients resulted in decreased mTg-specific T cell responses. Furthermore, lymphocytes obtained from these donors and recipients after adoptive transfer produced significantly higher levels of IL-10 compared with mTg-primed, untreated, control mice. Administration of anti-IL-10R Ab into GM-CSF-treated mice abrogated GM-CSF-induced suppression of EAT, as indicated by increased mTg-specific T cell responses, thyroid lymphocyte infiltration, and follicular destruction. Interestingly, in vivo blockade of IL-10R did not affect GM-CSF-induced expansion of CD4(+)CD25(+) T cells. However, IL-10-induced immunosuppression was due to its direct effects on mTg-specific effector T cells. Taken together, these results indicated that IL-10, produced by CD4(+)CD25(+) T cells that were probably induced by semimature DCs, is essential for disease suppression in GM-CSF-treated mice.
Gangi
Eryn
E
Departments of Microbiology, University of Illinois, Chicago, 60612, USA.
Vasu
Chenthamarakshan
C
Cheatem
Donald
D
Prabhakar
Bellur S
BS
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000096:biosynthesis*; D051379:Mice; D008808:Mice, Inbred CBA; D018123:Receptors, Interleukin / Q000276:immunology; D053701:Receptors, Interleukin-10; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D013954:Thyroglobulin / Q000008:administration & dosage / Q000276:immunology; D013961:Thyroid Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000276:immunology / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013954:Thyroglobulin