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Titolo:
Cell surface CD28 levels define four CD4(+) T cell subsets: Abnormal expression in rheumatoid arthritis
Autore:
Salazar-Fontana, LI; Sanz, E; Merida, I; Zea, A; Sanchez-Atrio, A; Villa, L; Martinez, C; de la Hera, A; Alvarez-Mon, M;
Indirizzi:
Univ Alcala, Fac Med, CSIC,Sch Med,Dept Med, Lab Immunol & Oncol,Ctr Invest Biol,Associated Un, Madrid 28871, Spain Univ Alcala Madrid Spain 28871 t Biol,Associated Un, Madrid 28871, Spain Prince Asturias Univ Hosp, Clin Immunol & Oncol Branch, Madrid 28871, Spain Prince Asturias Univ Hosp Madrid Spain 28871 Branch, Madrid 28871, Spain Ramon & Cajal Univ Hosp, Rheumatol Unit, Madrid 28034, Spain Ramon & CajalUniv Hosp Madrid Spain 28034 tol Unit, Madrid 28034, Spain CSIC, Ctr Nacl Biotecnol, Dept Immunol & Oncol, E-28049 Madrid, Spain CSIC Madrid Spain E-28049 l, Dept Immunol & Oncol, E-28049 Madrid, Spain
Titolo Testata:
CLINICAL IMMUNOLOGY
fascicolo: 2, volume: 99, anno: 2001,
pagine: 253 - 265
SICI:
1521-6616(200105)99:2<253:CSCLDF>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; LYMPHOCYTES-T; ACTIVATION PATHWAY; DOWN-REGULATION; SELF-TOLERANCE; IMMUNE-SYSTEM; 9.3 ANTIGEN; RECEPTOR; COSTIMULATION; INDUCTION;
Keywords:
rheumatoid arthritis; CD28 surface modulation; T-cell anergy; costimulatory molecules; CTLA-4; CD152; CD80; CD86; B7;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Alvarez-Mon, M Univ Alcala, Fac Med, CSIC,Sch Med,Dept Med, Lab Immunol & Oncol,Ctr Invest Biol,Associated Un, Ctra Madrid Barcelona Km 33, Madrid 28871, Spain Univ Alcala Ctra Madrid Barcelona Km 33 Madrid Spain 28871
Citazione:
L.I. Salazar-Fontana et al., "Cell surface CD28 levels define four CD4(+) T cell subsets: Abnormal expression in rheumatoid arthritis", CLIN IMMUNO, 99(2), 2001, pp. 253-265

Abstract

CD28 is a costimulatory receptor expressed in most CD4(+) T cells. Despitethe long-standing evidence for up- and downregulation of surface CD28 expression in vitro, and the key regulatory role assigned to the upregulation of CD28 counterreceptor [the CD152 (CTLA-4) molecule], in vivo CD28 induction has attracted little attention. We studied CD28 and CD152 expression and function in 33 rheumatoid arthritis (RA) patients, 20 clinically active and13 inactive, and in 24 healthy donors. Four subsets of CD28(-), CD28(low),CD28(int), and CD28(high) peripheral blood human CD4(+) T cells were defined using three-color flow cytometry, The three CD28(+) subsets displayed a one-, two-, or threefold quantitative difference in their relative number of CD28 antibody binding sites, respectively (P < 0.01), RA patients, whether active or inactive, showed a distinct phenotype when compared to healthy donors: (i) the percentage of CD4(+)CD28(high) cells was increased twofold and the CD4(+)CD281(low) subset was reduced twofold (P < 0.01) and (ii) theCD4(+)CD28(high) cells from RA patients showed an in vivo activated phenotype, CD45RO(+)CD5(high)IL-2R alpha (+) (P < 0.01). Active RA patients were different from inactive patients. They showed a twofold increase in mean CD28 expression (P < 0.05), whereas each of the CD28(+) subsets in the inactive RA patients showed reduced expression when compared to healthy donors, Notably, both active and inactive RA patients showed abnormal CD28 upregulation when T cells were activated in vitro with CD3 antibodies, but only inactive RA. patients showed a hypoproliferative response to TCR/CD3 triggeringwhen compared to healthy donors (P < 0.01), This defective proliferation was normalized by concurrent crosslinking with CD28 antibody, No differenceswere noted in the expression of CD152 or CD80, a CD28 and CD152 shared ligand. The disregulated in vivo expression of CD28 was related to the RA patients' disease activity and suggests that modulation of CD28 surface levels may be an additional mechanism to finely tune the delicate responsiveness/tolerance balance. (C) 2001 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 12:15:16