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Successful engraftment of human postnatal thymus in severe combined immune deficient (SCID) mice: differential engraftment of thymic components with irradiation versus anti-asialo GM-1 immunosuppressive regimens.

Publication ,  Journal Article
Barry, TS; Jones, DM; Richter, CB; Haynes, BF
Published in: J Exp Med
January 1, 1991

To develop a model of human thymus growth in vivo, we have implanted postnatal human thymus under the renal capsule of severe combined immune deficient (SCID) mice and assayed for graft survival and graft characteristics 1-3 mo after engraftment. Three groups of SCID mice were engrafted with postnatal human thymus: untreated SCID mice, SCID mice pretreated with 400 cGy of gamma irradiation 1-5 d before engraftment, and SCID mice treated with intraperitoneal anti-asialo GM-1 antiserum every 4-5 d during engraftment. In the untreated group of SCID mice, only 37% of grafts survived and consisted of human thymic microenvironment components and human immature thymocytes. Irradiation of SCID mice before engraftment improved survival of human thymic grafts to 83%, but these grafts were largely devoid of thymocytes and contained only thymic microenvironment components with large numbers of thymic macrophages. Treatment of SCID mice with anti-asialo GM-1 antiserum throughout the engraftment period also promoted human thymus engraftment (70%) and induced SCID B cell Ig production (SCID[Ig+]) in 38% of animals. In SCID(Ig-) anti-asialo GM-1-treated mice, the human thymic grafts were similar in content to those in untreated SCID mice. However, in anti-asialo GM-1-treated animals with grafts that became SCID(Ig+), all animals were found to have mouse-human chimeric grafts in that the human thymic microenvironment (human fibroblasts, thymic epithelium, vessels) was colonized by murine T cells. These data demonstrate that human postnatal thymus will grow as xenografts in SCID mice, and that the components of human thymus that engraft are dependent on the immunosuppressive regimen used in recipient mice. A striking finding in this study was the induction of T and B lymphopoiesis in SCID mice by abrogation of NK cell activity with in vivo anti-asialo GM-1 treatment. These data strongly suggest that asialo GM-1+ NK cells and/or macrophages play a role in mediation of suppression of lymphopoiesis in SCID mice.

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Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

January 1, 1991

Volume

173

Issue

1

Start / End Page

167 / 180

Location

United States

Related Subject Headings

  • Whole-Body Irradiation
  • Transplantation, Heterologous
  • Thymus Gland
  • T-Lymphocytes
  • Mice
  • Male
  • Infant, Newborn
  • Infant
  • Immunosuppression Therapy
  • Immunophenotyping
 

Citation

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Barry, T. S., D. M. Jones, C. B. Richter, and B. F. Haynes. “Successful engraftment of human postnatal thymus in severe combined immune deficient (SCID) mice: differential engraftment of thymic components with irradiation versus anti-asialo GM-1 immunosuppressive regimens.J Exp Med 173, no. 1 (January 1, 1991): 167–80. https://doi.org/10.1084/jem.173.1.167.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

January 1, 1991

Volume

173

Issue

1

Start / End Page

167 / 180

Location

United States

Related Subject Headings

  • Whole-Body Irradiation
  • Transplantation, Heterologous
  • Thymus Gland
  • T-Lymphocytes
  • Mice
  • Male
  • Infant, Newborn
  • Infant
  • Immunosuppression Therapy
  • Immunophenotyping