Characterization of long-term mixed donor-donor chimerism after double cord blood transplantation

• Published in: Clinical and experimental immunology 2010-10, Vol.162 (1), p.146-155
• Main Authors: Gertow, J, Berglund, S, Okas, M, Uzunel, M, Berg, L, Kärre, K, Mattsson, J, Uhlin, M
• Format: Article
• Language: English
• Subjects: allogeneic; Analytical, structural and metabolic biochemistry; Biological and medical sciences; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cells, Cultured; Chimerism; Cord blood; Cord Blood Stem Cell Transplantation - methods; cord blood transplantation; Cytokines; Donors; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Hematopoiesis - immunology; HLA-C; Humans; Immunologic Memory - immunology; Immunological memory; Interferon-gamma - metabolism; Interleukin-2 - metabolism; K562 Cells; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Leukocytes; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Lymphocytes T; Medicin och hälsovetenskap; Memory cells; Mitogens - pharmacology; mixed chimerism; Natural killer cells; SCT; Stem cells; Time Factors; Tissue Donors; Translational Studies; Transplantation Chimera - blood; Transplantation Chimera - immunology; Transplants & implants; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0009-9104; 1365-2249; 1365-2249
• DOI: 10.1111/j.1365-2249.2010.04212.x

Double cord blood transplantation (DCBT) with two matched or partially matched cord blood units has been implemented successfully to circumvent the limitations of graft cell dose associated with single CBT. After DCBT, sustained haematopoiesis is derived almost exclusively from only one of the donated units. None the less, we previously observed two of six evaluable DCBT patients still having mixed donor-donor chimerism at 28 and 45 months post-transplantation, respectively. In the present study we utilize flow cytometry techniques to perform the first thorough analysis of phenotype and functionality of cord blood units in patients with mixed donor-donor chimerism. Our results suggest that the two stable cord blood units are different phenotypically and functionally: one unit shows more naive T cells, lower T cell cytokine production and higher frequencies of natural killer cells, the other shows higher frequencies of well-differentiated and functional lymphocytes. Additionally, in comparison with control patients having a single prevailing cord blood unit, the patients with donor-donor chimerism exhibit less overall T cell cytokine production and a smaller fraction of memory T cells. Furthermore, our results indicate that human leucocyte antigen-C match of donor units may partly explain the development of a donor-donor mixed chimerism.