title: Activation of CD4⁺ Foxp3⁺ regulatory T cells proceeds normally in the absence of B cells during EAE.
abstract: B cells and regulatory T (Treg) cells can both facilitate remission from experimental auto immune encephalomyelitis (EAE), a disease of the central nervous system (CNS) used as a model for multiple sclerosis (MS). Considering that B-cell-depletion therapy (BCDT) is used to treat MS patients, we asked whether Treg-cell activation depended on B cells during EAE. Treg-cell proliferation, accumulation in CNS, and augmentation of suppressive activity in the CNS were normal in B-cell-deficient mice, indicating that B cells are not essential for activation of the protective Treg-cell response and thus provide an independent layer of regulation. This function of B cells involved early suppression of the encephalitogenic CD4(+)  T-cell response, which was enhanced in B-cell-deficient mice. CD4(+)  T-cell depletion was sufficient to intercept the transition from acute-to-chronic EAE when applied to B-cell-deficient animals that just reached the peak of disease severity. Intriguingly, this treatment did not improve disease when applied later, implying that chronic disability was ultimately maintained independently of pathogenic CD4(+)  T cells. Collectively, our data indicate that BCDT is unlikely to impair Treg-cell function, yet it might produce undesirable effects on T-cell-mediated autoimmune pathogenesis.
authors.affiliation: Deutsches Rheuma-ForschungsZentrum a Leibniz Institute, Berlin, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Hoehlig
authors.forename: Ping
authors.initials: P
authors.lastname: Shen
authors.forename: Vicky
authors.initials: V
authors.lastname: Lampropoulou
authors.forename: Toralf
authors.initials: T
authors.lastname: Roch
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Richard
authors.initials: R
authors.lastname: O'Connor
authors.forename: Stefanie
authors.initials: S
authors.lastname: Ries
authors.forename: Ellen
authors.initials: E
authors.lastname: Hilgenberg
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Anderton
authors.forename: Simon
authors.initials: S
authors.lastname: Fillatreau
mesh_terms: D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse