title: Peripheral blood lymphocytes in SLE--hyperexpression of CD154 on T and B lymphocytes and increased number of double negative T cells.
abstract: Abnormalities in the regulation of both cell-mediated and humoral immunity have been implicated in the pathophysiology of systemic lupus erythematosus (SLE). Cognate contact-dependent T-B cell interactions involving CD154 (CD40 ligand) on activated T cells and CD40 on B lymphocytes have a critical role in antibody production. Abnormal CD154 expression on lymphocytes may play a role in the production of potentially pathogenic autoantibodies and defects in self-tolerance mechanisms may be important. Failure of intrathymic or peripheral deletion of autoreactive T cells may also result in an autoimmune phenotype. Elevated levels of CD3(+)CD4(-)/8(-) (double negative) T cells (DNT) in the peripheral blood are a surrogate marker for defects of this type. The expression of CD154 on T and B cells was evaluated and levels of double negative T cells in the peripheral blood were assessed by two and three colour flow cytometric analyses. We studied peripheral blood lymphocytes in 48 patients with SLE. Twenty-five normal subjects and 12 patients with rheumatoid arthritis (RA) were studied as disease controls. T cells in 22/48 (45%) lupus patients expressed CD154 between 20-80% (median=52%). In normal controls and RA patients 8-18% T cells were CD154(+). Twelve patients (30%) had elevated expression of CD154 (20-50%) on B cells. In the control RA patients, less than 15% T cells were CD154(+). Twelve of 48 SLE patients had elevated numbers of DNT cells (18-27%). The control subjects had DNT cell numbers <10. These observations suggest that defects in either the intrathymic or peripheral deletion of potentially pathogenic T lymphocytes may play a role in the pathogenesis of SLE. The high expression of CD154 on both T and B cells may also be important in mediating the production of potentially harmful autoantibodies.
authors.affiliation: Division of Rheumatology, Imperial College of Science, Technology and Medicine, London, UK.
authors.forename: B S
authors.initials: BS
authors.lastname: Devi
authors.forename: S
authors.initials: S
authors.lastname: Van Noordin
authors.forename: T
authors.initials: T
authors.lastname: Krausz
authors.forename: K A
authors.initials: KA
authors.lastname: Davies
mesh_terms: D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000097:blood*; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D015704:CD4 Antigens / Q000097:blood; D023201:CD40 Ligand; D016827:CD8 Antigens / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood* / Q000276:immunology*; D008875:Middle Aged; D017634:Self Tolerance; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D001323:Autoantibodies; D015704:CD4 Antigens; D016827:CD8 Antigens; D008562:Membrane Glycoproteins; D023201:CD40 Ligand