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Lymphoid Reconstitution

Lymphocyte reconstitution following non-myeloablative hematopoietic stem cell transplantation follows two patterns depending on age and donor/recipient chimerism

Bone Marrow Transplantation volume 28, pages 463–471 (2001)Cite this article

Abstract

The effect of mixed chimerism on the pace of post-transplant immune reconstitution is unknown. Using flow cytometry, recall and neo-antigen vaccine responses, and T cell receptor recombination excision circle (TREC) quantification, we evaluated phenotypic and functional characteristics of T and B cells in nine patients following non-myeloablative, HLA-identical peripheral blood stem cell transplantation for chronic granulomatous disease. Engraftment of T cell, B cell, and myeloid lineages proceeded at similar paces within each patient, but engraftment kinetics segregated patients into two groups: adults, who became full donor T cell chimeras before 6 months (rapid engrafters) and children, who became full donor T cell chimeras after 6 months or not at all (slow engrafters). Quantitative B cell recovery was achieved by 6 weeks after transplantation in children, but was delayed until 1 year in adults. Early quantitative B cell recovery was not accompanied by an early humoral immune response to tetanus toxoid (TT). Emergence of TT-specific T cell responses coincided with naive T cell reconstitution, as measured by CD4/CD45RA T cell recovery and TREC quantification. These data suggest that immune reconstitution occurs faster in pediatric patients who have prolonged mixed hematopoietic chimerism compared to adults, who have rapid donor stem cell engraftment. Bone Marrow Transplantation (2001) 28, 463–471.

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Acknowledgements

This work was supported in part by the Clinical Research Training Program, a partnership between the Foundation for the NIH and Pfizer Inc, Leukemia and Lymphoma Society of America translational research grant 6540–00, and AMFAR grant 02680–28-RGV.

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Authors and Affiliations

  1. Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases (NIAID), National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    WJ Savage, GM Linton, HL Malech & ME Horwitz

  2. Department of Laboratory Medicine, Clinical Center, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    JJH Bleesing & MR Brown

  3. Vaccine Research Center, NIAID, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    D Douek

  4. Department of Experimental Transplantation and Immunology, Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    D Douek

  5. Weill Medical College of Cornell University, New York, NY, USA

    WJ Savage

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Savage, W., Bleesing, J., Douek, D. et al. Lymphocyte reconstitution following non-myeloablative hematopoietic stem cell transplantation follows two patterns depending on age and donor/recipient chimerism. Bone Marrow Transplant 28, 463–471 (2001). https://doi.org/10.1038/sj.bmt.1703176

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