title: The T-cell pool is anergized in patients with multiple sclerosis in remission.
abstract: Relapsing-remitting multiple sclerosis (RRMS) is a complex autoimmune disease of the central nervous system with oscillating phases of relapse and remission. RRMS has been considered to be driven by T helper type 1 (Th1) lymphocytes but new data indicate the involvement of Th17 responses. In the present study, blood samples from patients (n=48) and healthy individuals (n=44) were evaluated for their immunological status. T cells from patients with RRMS expressed high levels of the activation marker CD28 (P<0.05) and secreted both interferon-gamma (CD8: P<0.05) and interleukin-17 upon polyclonal mitogen or myelin oligodendrocyte glycoprotein antigen stimulation. However, T cells from patients with RRMS in remission, in contrast to relapse, had poor proliferative capacity (P<0.05) suggesting that they are controlled and kept in anergy. This anergy could be broken with CD28 stimulation that restored the T-cell replication. Furthermore, the patients with RRMS had normal levels of CD4(+) Foxp3(+) T regulatory cells but the frequency of Foxp3(+) cells lacking CD127 (interleukin-7 receptor) was lower in patients with MS (mean 12%) compared to healthy controls (mean 29%). Still, regulatory cells (CD25(+) sorted cells) from patients with RRMS displayed no difference in suppressive capacity. In conclusion, patients in relapse/remission demonstrate in vitro T-cell responses that are both Th1 and Th17 that, while in remission, appear to be controlled by tolerogenic mechanisms yet to be investigated.
authors.affiliation: Clinical Immunology Division, Uppsala University, Uppsala, Sweden. moa.fransson@klinimm.uu.se
authors.forename: Moa E
authors.initials: ME
authors.lastname: Fransson
authors.forename: Lina S E
authors.initials: LS
authors.lastname: Liljenfeldt
authors.forename: Jan
authors.initials: J
authors.lastname: Fagius
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Tötterman
authors.forename: Angelica S I
authors.initials: AS
authors.lastname: Loskog
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D020381:Interleukin-17; D053699:Interleukin-7 Receptor alpha Subunit; C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D007371:Interferon-gamma