title: Regulatory T and B lymphocytes in a spontaneous autoimmune polyneuropathy.
abstract: B7-2(-/-) non-obese diabetic (NOD) mice develop a spontaneous autoimmune polyneuropathy (SAP) that mimics the progressive form of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). In this study, we focused on the role of regulatory T cells (Tregs ) and regulatory B cells (Bregs ) in SAP. We found that deletion of B7-2 in female NOD mice led to a lower frequency and number of Tregs and Bregs in spleens and lymph nodes. Tregs but not Bregs suppressed antigen-stimulated splenocyte proliferation, whereas Bregs inhibited the T helper type 1 (Th1) cytokine response. Both Tregs and Bregs induced an increase in CD4(+) interleukin (IL)-10(+) cells, although less effectively in the absence of B7-2. Adoptive transfer studies revealed that Tregs , but not Bregs , suppressed SAP, while Bregs attenuated disease severity when given prior to symptom onset. B cell deficiency in B cell-deficient (muMT)/B7-2(-/-) NOD mice prevented the development of SAP, which would indicate that the pathogenic role of B cells predominates over its regulatory role in this model. We conclude that Bregs and Tregs control the immunopathogenesis and progression of SAP in a non-redundant fashion, and that therapies aimed at expansion of Bregs and Tregs may be an effective approach in autoimmune neuropathies.
authors.affiliation: Department of Neurology, The University of Chicago, Chicago, IL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Quan
authors.affiliation: Department of Neurology, The University of Chicago, Chicago, IL, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Sheng
authors.affiliation: Department of Neurology, The University of Chicago, Chicago, IL, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Abraham
authors.affiliation: Department of Neurology, The University of Chicago, Chicago, IL, USA.
authors.forename: B
authors.initials: B
authors.lastname: Soliven
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D051940:B7-2 Antigen / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D016688:Mice, Inbred NOD; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D058408:Th1-Th2 Balance
chemical_list: D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; C556062:IL10 protein, mouse; D016753:Interleukin-10
keywords: Bregs; CIDP; Guillain-Barré syndrome; Tregs; co-stimulatory molecules