title: The expanded double negative T cell populations of a patient with ALPS are not clonally related to CD4+ or to CD8+ T cells.
abstract: The autoimmune lymphoproliferative syndrome (ALPS) is characterized by non-malignant lymphoproliferation and signs of autoimmunity. A hallmark of ALPS are high amounts of circulating CD3+/CD4-/CD8- double negative T-lymphocytes (DN T cells). The origin of these cells remains elusive. To investigate the relationships of DN T cells and the single positive T cell populations (CD4+ and CD8+), we analyzed by spectratyping the complementarity determining regions 3 (CDR3) of the T cell receptors in sorted "single positive" (CD4+, CD8+) and DN T cells in a patient with ALPS type 1a. We observed signs for clonal expansion in all three T cell subpopulations. Strong and weak clonal expansions were to be seen in 16 and 14 for DN, 6 and 12 for CD8+, and 1 and 5 for CD4 + T cells, respectively. Most importantly, 24 out of 30 aberrant peaks in the spectratype histograms of the DN T cells where unique for this population and were not to be detected in the histograms of the single positive T cells. In contrast to published data, we conclude that expanded DN T cell populations in ALPS are not generally derived from expanded CD3+/CD4+ or CD3+/CD8+ populations.
authors.affiliation: Department of Internal Medicine 3, Institute of Clinical Immunology and Rheumatology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Arnold
authors.initials: A
authors.lastname: Marlies
authors.forename: Gaipl
authors.initials: G
authors.lastname: Udo
authors.forename: Brunner
authors.initials: B
authors.lastname: Juergen
authors.forename: Spriewald
authors.initials: S
authors.lastname: Bernd
authors.forename: Martin
authors.initials: M
authors.lastname: Herrmann
authors.forename: Johannes Peter
authors.initials: JP
authors.lastname: Haas
mesh_terms: D000328:Adult; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000473:pathology; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013577:Syndrome
chemical_list: D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell