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Titolo:
Myasthenia in SCID mice grafted with myasthenic patient lymphocytes - Roleof CD4(+) and CD8(+) cells
Autore:
Wang, ZY; Karachunski, PI; Howard, JF; Conti-Fine, BM;
Indirizzi:
Univ Minnesota, Coll Biol Sci, Dept Biochem, St Paul, MN 55108 USA Univ Minnesota St Paul MN USA 55108 , Dept Biochem, St Paul, MN 55108 USA Univ Minnesota, Sch Med, Dept Pharmacol, Minneapolis, MN 55455 USA Univ Minnesota Minneapolis MN USA 55455 rmacol, Minneapolis, MN 55455 USA Univ N Carolina, Dept Neurol, Chapel Hill, NC USA Univ N Carolina Chapel Hill NC USA ina, Dept Neurol, Chapel Hill, NC USA
Titolo Testata:
NEUROLOGY
fascicolo: 3, volume: 52, anno: 1999,
pagine: 484 - 497
SICI:
0028-3878(199902)52:3<484:MISMGW>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
SEVERE COMBINED IMMUNODEFICIENCY; MUSCLE ACETYLCHOLINE-RECEPTOR; T-CELLS; EPITOPE REPERTOIRE; ALPHA-SUBUNIT; SEQUENCE SEGMENTS; GRAVIS; MOUSE; MODEL; DEFICIENCY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Conti-Fine, BM Univ55108esota, Coll Biol Sci, Dept Biochem, 1479 Gortner Ave, St Paul, MN Univ Minnesota 1479 Gortner Ave St Paul MN USA 55108 ul, MN
Citazione:
Z.Y. Wang et al., "Myasthenia in SCID mice grafted with myasthenic patient lymphocytes - Roleof CD4(+) and CD8(+) cells", NEUROLOGY, 52(3), 1999, pp. 484-497

Abstract

Objectives: Acetylcholine receptor (AChR)-specific CD4(+) cells are present in MG patients, and synthesis of the high-affinity immunoglobulin G (IgG)autoantibodies (autoAb) against the muscle AChR that causes MG symptoms requires intervention of CD4(+) cells. The role of CD4(+) cells in MG pathogenesis has been postulated but never proven. MG patients do not have anti-AChR cytotoxic phenomena, and it has been assumed that CD8(+) cells do not have a pathogenic role in MG. However, CD8(+) cells may facilitate rodent experimental MG, raising the possibility that CD8(+) cells might be necessary also in MG. In this study we examined whether CD4(+) and CD8(+) cells play a role in the pathogenesis of MG and whether CD4(+) cells specific for AChRepitope sequences recognized by most MG patients ("universal" epitopes) drive the synthesis of pathogenic antibodies. Methods: First we characterizeda chimeric human-mouse model of MG in severe combined immunodeficiency (SCID) mice engrafted with blood lymphocytes (BL) from MG patients. We used that model to determine whether CD4(+) and CD8(+) cells are necessary for transfer of MG symptoms. We engrafted SCID mice intraperitoneum with BL from 19 MG patients and 5 healthy controls. We engrafted some mice with either BL, BL depleted in CD4(+) or CD8(+) cells from the same patient, or CD4(+) depleted BL reconstituted with CD4(+) T cells from the same patient, specificfor "universal" AChR epitopes or for two unrelated antigens, tetanus and diphtheria toxoids. We tested the mice for myasthenic symptoms for 7 to 18 weeks. Results: Mice transplanted with BL, or CD8(+) depleted BL, or CD4(+)-depleted BL reconstituted with anti-AChR CD4(+) cells from MG patients frequently developed myasthenic weakness. The mice had human anti-AChR Ab in the serum and bound to muscle AChR. Mice transplanted with BL from controls, or CD4(+)-depleted BL from MG patients, or CD4(+)-depleted BL from an MG patient reconstituted with CD4(+) cells specific for tetanus or diphtheria toxoids did not develop myasthenic weakness or anti-AChR Ab. Conclusions: CD4(+)cells are necessary for MG pathogenesis; CD8(+) cells may not be. CD4(+)cells specific for "universal" AChR epitopes help the synthesis of pathogenic Ab.

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Documento generato il 05/12/20 alle ore 23:56:25