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Prepublished online as a Blood First Edition Paper on April 10, 2003; DOI 10.1182/blood-2002-09-2755.

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2002-09-2755v1
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Blood, 1 August 2003, Vol. 102, No. 3, pp. 873-880

HEMATOPOIESIS

Complete reconstitution of human lymphocytes from cord blood CD34+ cells using the NOD/SCID/{gamma}cnull mice model

Hidefumi Hiramatsu, Ryuta Nishikomori, Toshio Heike, Mamoru Ito, Kimio Kobayashi, Kenji Katamura, and Tatsutoshi Nakahata

From the Department of Pediatrics, Graduate School of Medicine, Kyoto University; and the Central Institute for Experimental Animals, Kawasaki, Japan

Establishment of an assay capable of generating all classes of human lymphocytes from hematopoietic stem cells (HSCs) will provide new insight into the mechanism of human lymphopoiesis. We report ontogenic, functional, and histologic examination results of reconstituted human lymphocytes in NOD/SCID/ {gamma}cnull mice after the transplantation of human cord blood (CB) CD34+ cells. After transplantation, human B, natural killer (NK), and T cells were invariably identified in these mice, even though no human tissues were cotransplanted. Immature B cells resided mainly in bone marrow (BM), whereas mature B cells with surface immunoglobulins were preferentially found in spleen. NK cells were identified in BM and spleen. T cells were observed in various lymphoid organs, but serial examinations after transplantation confirmed human T lymphopoiesis occurring in the thymus. These human lymphocytes were also functionally competent. Human immunoglobulin M (IgM), IgA, and IgG were detected in the sera of these mice. T cells showed a diverse repertoire of T-cell–receptor V{beta} (TCR V{beta}) chains, proliferated in response to phytohemagglutinin, and were cytotoxic against cell lines. NK activity was demonstrated using the K562 cell line. Immunohistochemical analysis revealed that human lymphocytes formed organized structures in spleen and thymus that were analogous to those seen in humans. In the thymus, CD4 and CD8 double-positive T cells were predominant and coexpressed CD1a and Ki-67, thereby supporting the notion that T lymphopoiesis was taking place. NOD/SCID/ {gamma}cnull mice provide a unique model to investigate human lymphopoiesis without the cotransplantation of human tissues.


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