B cell-deficient NOD.H-2h4 mice have CD4+CD25+ T regulatory cells that inhibit the development of spontaneous autoimmune thyroiditis.
Wild-type (WT) NOD.H-2h4 mice develop spontaneous autoimmune thyroiditis (SAT) when given 0.05% NaI in their drinking water, whereas B cell-deficient NOD.H-2h4 mice are SAT resistant. To test the hypothesis that resistance of B cell-deficient mice to SAT was due to the activity of regulatory CD4+CD25+ T (T reg) cells activated if autoantigen was initially presented on non-B cells, CD25+ T reg cells were transiently depleted in vivo using anti-CD25. B cell-deficient NOD.H-2h4 mice given three weekly injections of anti-CD25 developed SAT 8 wk after NaI water. Thyroid lesions were similar to those in WT mice except there were no B cells in thyroid infiltrates. WT and B cell-deficient mice had similar numbers of CD4+CD25+Foxp3+ cells. Mice with transgenic nitrophenyl-specific B cells unable to secrete immunoglobulin were also resistant to SAT, and transient depletion of T reg cells resulted in severe SAT with both T and B cells in thyroid infiltrates. T reg cells that inhibit SAT were eliminated by day 3 thymectomy, indicating they belong to the subset of naturally occurring T reg cells. However, T reg cell depletion did not increase SAT severity in WT mice, suggesting that T reg cells may be nonfunctional when effector T cells are activated; i.e., by autoantigen-presenting B cells.
Yu
Shiguang
S
Department of Medicine, University of Missouri, Columbia, MO 65212, USA.
Maiti
Prasanta K
PK
Dyson
Melissa
M
Jain
Renu
R
Braley-Mullen
Helen
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007136:Immunoglobulins / Q000172:deficiency; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000235:genetics* / Q000276:immunology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007136:Immunoglobulins; D015375:Receptors, Interleukin-2