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Titolo:
IMMUNOMODULATION OF AUTOIMMUNITY IN MRL LPR MICE WITH SYNGENEIC BONE-MARROW TRANSPLANTATION (SBMT)/
Autore:
KARUSSIS DM; VOURKAKARUSSIS U; LEHMANN D; ABRAMSKY O; BENNUN A; SLAVIN S;
Indirizzi:
HADASSAH HEBREW UNIV HOSP,DEPT NEUROL IL-91120 JERUSALEM ISRAEL HADASSAH HEBREW UNIV HOSP,DEPT BONE MARROW TRANSPLANTAT IL-91120 JERUSALEM ISRAEL HADASSAH HEBREW UNIV HOSP,CANC RES LAB IL-91120 JERUSALEM ISRAEL WEIZMANN INST SCI,DEPT CELL BIOL IL-76100 REHOVOT ISRAEL
Titolo Testata:
Clinical and experimental immunology
fascicolo: 1, volume: 100, anno: 1995,
pagine: 111 - 117
SICI:
0009-9104(1995)100:1<111:IOAIML>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
TOTAL LYMPHOID IRRADIATION; RHEUMATOID-ARTHRITIS; LUPUS NEPHRITIS; MURINE LUPUS; PRONE MICE; DISEASE; ENCEPHALOMYELITIS; CYCLOPHOSPHAMIDE; TOLERANCE; REVERSAL;
Keywords:
MRL/LPR MICE; BONE MARROW TRANSPLANTATION; CYCLOPHOSPHAMIDE; TOTAL BODY IRRADIATION; SYSTEMIC LUPUS ERYTHEMATOSUS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
33
Recensione:
Indirizzi per estratti:
Citazione:
D.M. Karussis et al., "IMMUNOMODULATION OF AUTOIMMUNITY IN MRL LPR MICE WITH SYNGENEIC BONE-MARROW TRANSPLANTATION (SBMT)/", Clinical and experimental immunology, 100(1), 1995, pp. 111-117

Abstract

MRL-lpr/lpr mice spontaneously develop a severe autoimmune syndrome, characterized by massive generalized lymphadenopathy, arthritis, arteritis, dermatitis and immune complex-mediated glomerulonephritis. Bone marrow transplantation (BMT) from MHC-matched systemic lupus erythematosus (SLE)-resistant donors to susceptible recipients has proved effective in correcting autoimmune manifestations in autoimmune-prone mice. We investigated the effect of syngeneic BMT from MRL/lpr (donor) to immunocompromised MRL/lpr (recipient), after purging the bone marrow inoculum with MoAbs against mature T cells (anti-Thy 1.2). All the untreated mice developed lymphadenopathy and by the age of 36 weeks five ofthe eight were dead; in contrast, all the mice which underwent syngeneic BMT following acute immunosuppression with total body irradiation (900 cGy) (TBI) remained disease-free. In an additional experiment, itwas found that conditioning with cyclophosphamide (CY) before BMT wasmore effective than TBI in inhibiting delayed-onset autoimmune manifestations (mean survival 350 days in the CY group and 305 days in the TBI group, versus 197 days in untreated controls). Under both immunosuppressive regimens T cell-depleted bone marrow grafts produced far better results than did unmanipulated BMT. Following syngeneic BMT the incidence of proteinuria and the level of serum anti-DNA (dd) antibodies were significantly reduced, compared with that of the age-matched untreated controls. CY was more effective than TBI in reducing the anti-DNA titres. Likewise, T depletion of bone marrow inocula before BMT induced a more drastic drop in autoantibodies, following both CY and TBI conditioning protocols. After syngeneic BMT (either CY or TBI) no signsof lymphadenopathy were observed even at an advanced age. Upon histopathological examination, the BMT-treated mice displayed normal glomeruli with occasional minimal signs of glomerulonephritis. Syngeneic T cell-depleted BMT following acute cytoreduction of anti-self immune lymphocytes may represent a new therapeutic approach for drug-resistant autoimmune diseases.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 15:17:04