Intrathymic injection of hematopoietic progenitor cells establishes functional T cell development in a mouse model of severe combined immunodeficiency

Journal of Hematology & Oncology
Andrea Z TuckettJohannes L Zakrzewski

Abstract

Even though hematopoietic stem cell transplantation can be curative in patients with severe combined immunodeficiency, there is a need for additional strategies boosting T cell immunity in individuals suffering from genetic disorders of lymphoid development. Here we show that image-guided intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγnull mice is feasible and facilitates the generation of functional T cells conferring protective immunity. Hematopoietic stem and progenitor cells were isolated from the bone marrow of healthy C57BL/6 mice (wild-type, Luciferase+, CD45.1+) and injected intravenously or intrathymically into both male and female, young or aged NOD-scid IL2rγnull recipients. The in vivo fate of injected cells was analyzed by bioluminescence imaging and flow cytometry of thymus- and spleen-derived T cell populations. In addition to T cell reconstitution, we evaluated mice for evidence of immune dysregulation based on diabetes development and graft-versus-host disease. T cell immunity following intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγnull mice was assessed in a B cell lymphoma model. Despite the small size of the thymic remnant in NOD-scid IL2...Continue Reading

References

Jan 1, 1992·Advances in Immunology·H Kikutani, S Makino
Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·H R RodewaldC Haller
Mar 22, 2002·Nature Reviews. Immunology·G Anderson, E J Jenkinson
Aug 3, 2002·Nature Reviews. Immunology·Alain FischerMarina Cavazzana-Calvo
Dec 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yu-An CaoChristopher H Contag
Mar 18, 2005·Annual Review of Immunology·Mark S Anderson, Jeffrey A Bluestone
May 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Leonard D ShultzRupert Handgretinger
Sep 22, 2005·Proceedings of the National Academy of Sciences of the United States of America·Oumeya AdjaliNaomi Taylor
Nov 9, 2005·Mechanisms of Development·William E JenkinsonGraham Anderson
Dec 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Anna Morena D'AliseDiane Mathis
Sep 16, 2011·Scandinavian Journal of Immunology·I CaramalhoJ Demengeot
Jul 31, 2014·The New England Journal of Medicine·Sung-Yun PaiRichard J O'Reilly

❮ Previous
Next ❯

Citations

Jul 6, 2018·Journal of Hematology & Oncology·Dimitri KasakovskiYangqiu Li
Jul 20, 2019·Balsaeng'gwa saengsig·Ji Yoon LeeDong Ryul Lee
Sep 13, 2019·The Journal of Allergy and Clinical Immunology·Marie PouzollesValérie S Zimmermann
Dec 13, 2019·The Journal of Allergy and Clinical Immunology·Gregori Silvia, Aiuti Alessandro
Aug 24, 2021·Frontiers in Immunology·Aida KarachiMaryam Rahman
Nov 16, 2021·Acta Diabetologica·Andrea CoppolaMassimo Venturini

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
FCS
flow cytometry

Software Mentioned

GraphPad
Prism
Zeiss ZEN
FACSDiva
Panoramic Viewer
ImageJ

Related Concepts

Related Feeds

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.