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Titolo:
In utero bone marrow transplantation induces donor-specific tolerance by acombination of clonal deletion and clonal anergy
Autore:
Kim, HB; Shaaban, AF; Milner, R; Fichter, C; Flake, AW;
Indirizzi:
Childrensia,sp Philadelphia, Childrens Inst Surg Sci, Dept Surg, Philadelph Childrens Hosp Philadelphia Philadelphia PA USA 19104 pt Surg, Philadelph
Titolo Testata:
JOURNAL OF PEDIATRIC SURGERY
fascicolo: 5, volume: 34, anno: 1999,
pagine: 726 - 729
SICI:
0022-3468(199905)34:5<726:IUBMTI>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
HEMATOPOIETIC STEM-CELLS; MLSA-ENCODED ANTIGENS; NEONATAL TOLERANCE; MICE; ELIMINATION; REACTIVITY; INDUCTION; CHIMERAS;
Keywords:
in utero bone marrow transplantation; tolerance; clonal deletion; clonal anergy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
14
Recensione:
Indirizzi per estratti:
Indirizzo: Flake, AW ChildrensCivsp Philadelphia, Childrens Inst Surg Sci, Dept Surg,34th St & Childrens Hosp Philadelphia 34th St & Civ Ctr Blvd Philadelphia PA USA 19104
Citazione:
H.B. Kim et al., "In utero bone marrow transplantation induces donor-specific tolerance by acombination of clonal deletion and clonal anergy", J PED SURG, 34(5), 1999, pp. 726-729

Abstract

Background/Purpose: In utero bone marrow transplantation can induce donor-specific tolerance to postnatal solid organ transplantation, although the mechanisms remain poorly defined. in this study, we investigated the role ofclonal deletion and clonal anergy in the maintenance of tolerance in a murine model of in utero bone marrow transplantation. Methods: DBA/2 mice (Mls(a+)) were used as donors of adult bone marrow, and 14-day-gestation fetal Balb/c mice (Mls(s-)) were used as recipients. Tolerance was defined by donor-specific skin graft survival for more than 8 weeks. Clonal deletion was assessed by flow cytometry for V beta 6 T cell receptor usage. A tolerant animal demonstrating partial deletion of CD4+/V beta 6+ T cells and a nontolerant animal were selected for analysis of clonal anergy by a proliferation assay using plate-bound anti-V beta 6 antibody for stimulation with or without exogenous interleukin-2 (IL2). Results: V beta 6+ splenocytes constituted 6.32% of CD4(+) T cells in the tolerant animal compared with 9.19% in the nontolerant animal, demonstrating incomplete clonal deletion in the tolerant animal. Stimulation with plate-bound anti-VPG induced a good proliferative response in the nontolerant animal but a significantly attenuated response in the tolerant animal (P < .001), which was abrogated by the addition of IL2. Conclusions: In this murine model of in utero bone marrow transplantation,the tolerant state is characterized by partial clonal deletion of donor reactive T cells and clonal anergy of nondeleted donor reactive T cells. The anergic state can be abrogated by exogenous IL2, suggesting that the mechanism of a nergy is a deficiency of IL2 production. Copyright (C) 1999 by W.B. Saunders Company.

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Documento generato il 25/11/20 alle ore 09:31:22