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CD8a‐DCs induced upon GM‐CSF treatment can cause expansion of Tregs and suppress experimental autoimmune thyroiditis
Author(s) -
Prabhakar Bellur S,
Vasu Chentamarakshan,
Ganesh Balaji
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.669.10
Subject(s) - foxp3 , immunology , adoptive cell transfer , medicine , autoimmune thyroiditis , il 2 receptor , thyroiditis , effector , regulatory t cell , antigen presentation , immune system , t cell , thyroid
Experimental Autoimmune Thyroiditis (EAT) is a well characterized mouse model for Hashimoto's thyroiditis. Earlier, we reported that GM‐CSF treatment of mice with EAT can cause an expansion of CD8a‐DCs and CD4+CD25+ T cells with the ability to produce enhanced levels of IL‐10 and suppress the disease. Neither the underlying mechanism of action of GM‐CSF induced CD8a‐DCs (GM‐CD8a‐DCs), nor the regulatory phenotype of CD4+CD25+ T cells was explored. In this study, we show that GM‐CSF treatment can cause significant induction of Foxp3+ and IL‐10+ Tregs. Further, we show that GM‐CD8a‐DCs remain semi‐mature and are more tolerogenic relative to controls. These semi‐mature GM‐CD8a‐DCs showed lower transcript levels for TNF‐á, IL‐12, and IL1â. Antigen presentation by GM‐CD8a‐DCs caused significant expansion of Foxp3+ Tregs that could suppress effector T cell function through enhanced IL‐10. Adoptive transfer of CD8a‐DCs from GM‐CSF treated, but not untreated, SCID mice into CBA/J mice prevented EAT development. Our results show that GM‐CD8a‐DCs are tolerogenic in that antigen presentation by them can cause expansion of IL‐10+ and Foxp3+ Tregs that protect mice from developing EAT.