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Titolo:
Purified hematopoietic stem cell grafts induce tolerance to alloantigens and can mediate positive and negative T cell selection
Autore:
Shizuru, JA; Weissman, IL; Kernoff, R; Masek, M; Scheffold, YC;
Indirizzi:
Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 Med, Dept Med, Stanford, CA 94305 USA Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA Stanford UnivStanford CA USA 94305 , Dept Pathol, Stanford, CA 94305 USA
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 17, volume: 97, anno: 2000,
pagine: 9555 - 9560
SICI:
0027-8424(20000815)97:17<9555:PHSCGI>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR VIRUS SUPERANTIGENS; THYMIC EPITHELIUM; TRANSPLANTATION TOLERANCE; CLONAL DELETION; H-2 ANTIGENS; MICE; LYMPHOCYTES; SPECIFICITY; REPERTOIRE; RECEPTOR;
Keywords:
bone marrow transplantation; MHC restriction; mice;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Shizuru, JA Stanford Univ, Med Ctr, Dept Med, Div Bone Marrow Transplantat, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 t, Stanford, CA 94305 USA
Citazione:
J.A. Shizuru et al., "Purified hematopoietic stem cell grafts induce tolerance to alloantigens and can mediate positive and negative T cell selection", P NAS US, 97(17), 2000, pp. 9555-9560

Abstract

Engraftment of allogeneic bone marrow (BM) has been shown to induce tolerance to organs genotypically matched with the PM donor. Immune reconstitution after BM transplantation therefore involves re-establishment of a T cell pool tolerant to antigens present on both donor and host tissues. However, how hematopoietic grafts exert their influence over the regenerating immunesystem is not completely understood. Prior studies suggest that education of the newly arising T cell pool involves distinct contributions from donorand host stromal elements. Specifically, negative selection is thought to be mediated primarily by donor PM-derived antigen-presenting cells, whereaspositive selection is dictated by radio-resistant host-derived thymic stromal cells. In this report we studied the effect of highly purified allogeneic hematopoietic stem cells (HSCs) on organ transplantation tolerance induction and immune reconstitution. In contrast to engraftment of BM that results in near-complete donor T cell chimerism, HSC engraftment results in mixed T cell chimerism. Nonetheless we observed that HSC grafts induce tolerance to donor-matched neonatal heart grafts, and one way the HSC grafts alter host immune responses is via deletion of newly arising donor as well as radiation-resistant host T cells. Furthermore, using an in vivo assay of graft: rejection to study positive selection we made the unexpected observation that T cells in chimeric mice rejected grafts only in the context of the donor MHC type. These latter findings conflict with the conventionally held view that radio-resistant host elements primarily dictate positive selection.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/08/20 alle ore 00:49:56