title: Reduced T-cell repertoire restrictions in abatacept-treated rheumatoid arthritis patients.
abstract: BACKGROUND
  CD28(neg) T cells, which display functional characteristic of oligoclonally expanded cytotoxic memory T lymphocytes, are believed to be pathologically relevant in rheumatoid arthritis manifestation. The CD28 co-stimulation blockade by abatacept can prevent the generation of CD28(neg) T-cell populations in these patients.
  
  
  METHODS
  Samples were obtained before and after 12 months of abatacept therapy. T-cell phenotype and T-cell receptor diversity were evaluated by flow cytometry and complementarity-determining region-3 spectratyping, respectively, while telomerase reverse-transcriptase gene level was measured by real-time PCR.
  
  
  RESULTS
  Abatacept induces a decrease of the percentage and number of CD4(+)CD28(neg) T cells and a reduction of T-cell repertoire restrictions; these features are directly correlated. Thymic output and telomerase activity are not modified by the therapy.
  
  
  CONCLUSIONS
  Abatacept-induced decrease of peripheral T-cell repertoire restrictions can due to a reduced generation of senescent, chronically stimulated CD4(+)CD28(neg) T cells.
authors.affiliation: Centro Ricerca Emato-oncologica AIL (CREA), Diagnostics Department, Spedali Civili of Brescia, p.le Spedali Civili di Brescia, 1, 25123, Brescia, Italy. limberti@yahoo.it.
authors.forename: Luisa
authors.initials: L
authors.lastname: Imberti
authors.affiliation: Rheumatology and Clinical Immunology, Spedali Civili of Brescia, Brescia, Italy. mirko_scarsi@libero.it.
authors.forename: Mirko
authors.initials: M
authors.lastname: Scarsi
authors.affiliation: Centro Ricerca Emato-oncologica AIL (CREA), Diagnostics Department, Spedali Civili of Brescia, p.le Spedali Civili di Brescia, 1, 25123, Brescia, Italy. cinzia.zanotti@izsler.it.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Zanotti
authors.affiliation: Centro Ricerca Emato-oncologica AIL (CREA), Diagnostics Department, Spedali Civili of Brescia, p.le Spedali Civili di Brescia, 1, 25123, Brescia, Italy. marco_chiarini@dfci.harvard.edu.
authors.forename: Marco
authors.initials: M
authors.lastname: Chiarini
authors.affiliation: Centro Ricerca Emato-oncologica AIL (CREA), Diagnostics Department, Spedali Civili of Brescia, p.le Spedali Civili di Brescia, 1, 25123, Brescia, Italy. bert.diego@gmail.com.
authors.forename: Diego
authors.initials: D
authors.lastname: Bertoli
authors.affiliation: Rheumatology and Clinical Immunology, Spedali Civili of Brescia, Brescia, Italy. angela.tincani@unibs.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Tincani
authors.affiliation: Rheumatology and Clinical Immunology, Spedali Civili of Brescia, Brescia, Italy. airo@bresciareumatologia.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Airò
mesh_terms: D000069594:Abatacept / Q000494:pharmacology / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019098:Telomerase / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000069594:Abatacept; C509186:TERT protein, human; D019098:Telomerase