title: Circulating subsets and CD4(+)CD25(+) regulatory T cell function in chronic inflammatory demyelinating polyradiculoneuropathy.
abstract: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory disease of the peripheral nervous system that is probably autoimmune in origin. Different components of the adaptive and innate immunity may be responsible for the aberrant response towards nerve antigens. To investigate this, we examined lymphocyte subsets and regulatory T cell (Treg) function in the blood of CIDP patients, healthy controls (HC) and subjects with non-immune mediated neuropathies (other neuropathies, ON). We used flow cytometry to determine the frequency of monocytes, B cells, natural killer (NK) and NK-T cells, total and activated CD4(+) and CD8(+) T cells, effector memory and central memory CD4(+) and CD8(+) T cells, and CD4(+)CD25(high)Foxp3(+) Tregs. Treg function was studied after polyclonal stimulation and antigen specific stimulation with myelin protein peptides in CIDP and HC. There was an increased frequency of monocytes (p = 0.02) and decreased frequency of NK cells (p = 0.02) in CIDP compared with HC but not ON. There were no significant differences in other populations. Treg function was impaired in CIDP compared to HC (p = 0.02), whilst T cell proliferation to myelin protein peptides before and after depletion of Tregs was not different between patients and controls. This study shows increased circulating monocytes and reduced NK cells in CIDP. Although Treg frequency was not altered, we confirm that Tregs display a defect of suppressive function. Myelin protein peptides were not the target of the altered peripheral regulation of the immune response. The mechanisms of peripheral immune tolerance in CIDP and their relevance to the pathogenesis deserve further exploration.
authors.affiliation: Department of Clinical Neuroscience, King's College London, Guy's Hospital, London, UK. lara.sanvito@gmail.com
authors.forename: Lara
authors.initials: L
authors.lastname: Sanvito
authors.forename: Anna
authors.initials: A
authors.lastname: Makowska
authors.forename: Norman
authors.initials: N
authors.lastname: Gregson
authors.forename: Raffaello
authors.initials: R
authors.lastname: Nemni
authors.forename: Richard A C
authors.initials: RA
authors.lastname: Hughes
mesh_terms: D000328:Adult; D000368:Aged; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D009185:Myelin Proteins / Q000276:immunology; D055611:Natural Killer T-Cells / Q000166:cytology; D010446:Peptide Fragments / Q000276:immunology; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000097:blood / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D055815:Young Adult
chemical_list: D017252:CD3 Complex; D009185:Myelin Proteins; D010446:Peptide Fragments