Prenatal tolerance induction: relationship between cell dose, marrow T-cells, chimerism, and tolerance.

Cell Transplantation
Jeng-Chang ChenMing-Ling Kuo

Abstract

It was reported that the dose of self-antigens can determine the consequence of deletional tolerance and donor T cells are critical for tolerance induction in mixed chimeras. This study aimed at assessing the effect of cell doses and marrow T cells on engraftment and tolerance induction after prenatal bone marrow transplantation. Intraperitoneal cell transplantation was performed in FVB/N (H-2K(q)) mice at gestational day 14 with escalating doses of adult C57BL/6 (H-2K(b)) marrows. Peripheral chimerism was examined postnatally by flow cytometry and tolerance was tested by skin transplantation. Transplantation of light-density marrow cells showed a dose response. High-level chimerism emerged with a threshold dose of 5.0 x 10(6) and host leukocytes could be nearly replaced at a dose of 7.5-10.0 x 10(6). High-dose transplants conferred a steady long-lasting donor-specific tolerance but were accompanied by >50% incidence of graft-versus-host disease. Depletion of marrow T cells lessened graft-versus-host disease to the detriment of engraftment. With low-level chimerism, tolerance was a graded phenomenon dependent upon the level of chimerism. Durable chimerism within 6 months required a threshold of > or = 2% chimerism at 1 month of...Continue Reading

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Citations

Nov 11, 2010·Transplant International : Official Journal of the European Society for Organ Transplantation·Jinpu YuXishan Hao
Jan 9, 2013·The Journal of Surgical Research·Jeng-Chang ChenMing-Ling Kuo
Jun 1, 2013·Chimerism·Jeff E Mold, Colin C Anderson
Apr 12, 2016·American Journal of Respiratory and Critical Care Medicine·Jeng-Chang ChenMing-Ling Kuo
Nov 26, 2010·Cell Transplantation·S W Steven ShawAnna L David
Dec 10, 2008·Blood·Marcus O Muench
May 4, 2021·Frontiers in Immunology·Jeng-Chang Chen

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