| | |  | | | | Record from Web of Science® | | | | | | |
| ROLE OF INTRATHYMIC CLONAL DELETION AND PERIPHERAL ANERGY IN TRANSPLANTATION TOLERANCE INDUCED BY BONE-MARROW TRANSPLANTATION IN MICE CONDITIONED WITH A NONMYELOABLATIVE REGIMEN |
|
|
| Author(s): TOMITA Y, KHAN A, SYKES M |
| Source: JOURNAL OF IMMUNOLOGY Volume: 153 Issue: 3 Pages: 1087-1098 Published: AUG 1 1994 |
| Times Cited: 205 References: 64 |
| Abstract: We have investigated the mechanism of tolerance induced by allogeneic bone marrow transplantation (BMT) in mice conditioned with a nonmyeloablative regimen. Permanent mixed chimerism and skin allograft tolerance were achieved when recipient B10 (H-2(b)) mice were pre-treated with anti-CD4 and anti-CD8 mAbs, thymic irradiation, and 3 Gy whole body irradiation, followed by injection of B10.A (H-2(a)) bone marrow cells. V beta 11(+) T cells are normally deleted in I-E(+) B10.A mice, but not in I-E(-) B10 mice. In spleens of mixed B10.A-->B10 chimeras, V beta 11(+) B10 T cells were reduced but detectable in the first 6 wk after BMT, and later became undetectable. Splenic V beta 11+ T cells were unresponsive to receptor cross-linking with V beta 11-specific mAb, demonstrating anergy. B10 V beta 11(+) T cells were also detected in spleens of mice that were thymectomized before BMT. In PBL of chimeras, V beta 11(+) T cells were undetectable for at least 1.5 yr. Thymocyte chimerism and extensive clonal deletion of mature V beta 11(+) B10 thymocytes were observed as early as 10 days post-BMT and at all subsequent time points in thymi of mixed chimeras. Rare I-E(+) donor cells were detected in day 10 thymi, and these increased progressively in frequency at later times. In chimeras prepared in the reciprocal strain combination, B10-->B10.A, B10 donor V beta 11(+) T cells were undetectable in PBL. Together, our results implicate both central clonal deletion and peripheral clonal anergy in tolerance induced with our regimen. A very low number of intrathymic donor cells or low density of Ag expression is sufficient to mediate extensive clonal deletion of thymocytes that recognize donor Ags. |
| Document Type: Article |
| Language: English |
Addresses:
1. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, TRANSPLANTAT BIOL RES CTR, SURG SERV, BOSTON, MA 02129 USA |
| Publisher: AMER ASSOC IMMUNOLOGISTS, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Immunology |
| IDS Number: NY342 |
| ISSN: 0022-1767 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |