Delayed immune reconstitution after cord blood transplantation is characterized by impaired thymopoiesis and late memory T-cell skewing

Krishna V. Komanduri, Lisa S. St. John, Marcos De Lima, John McMannis, Steven Rosinski, Ian McNiece, Susan G. Bryan, Indreshpal Kaur, Sean Martin, Eric D. Wieder, Laura Worth, Laurence J.N. Cooper, Demetrios Petropoulos, Jeffrey J. Molldrem, Richard E. Champlin, Elizabeth J. Shpall

Research output: Contribution to journalArticle

212 Scopus citations

Abstract

Advances in immune assessment, including the development of T-cell receptor excision circle (TREC) assays of thymopoiesis, cytokine-flow cytometry assays of T-cell function, and higher-order phenotyping of T-cell maturation subsets have improved our understanding of T-cell homeostasis. Limited data exist using these methods to characterize immune recovery in adult cord blood (CB) transplant recipients, in whom infection is a leading cause of mortality. We now report the results of a single-center prospective study of T-cell immune recovery after cord blood transplantation (CBT) in a predominantly adult population. Our primary findings include the following: (1) Prolonged T lymphopenia and compensatory expansion of B and natural killer (NK) cells was evident; (2) CB transplant recipients had impaired functional recovery, although we did observe posttransplantation de novo T-cell responses to cytomegalovirus (CMV) in a subset of patients; (3) Thymopoietic failure characterized post-CBT immune reconstitution, in marked contrast to results in other transplant recipients; and (4) Thymopoietic failure was associated with late memory T-cell skewing. Our data suggest that efforts to improve outcomes in adult CB transplant recipients should be aimed at optimizing T-cell immune recovery. Strategies that improve the engraftment of lymphoid precursors, protect the thymus during pretransplant conditioning, and/or augment the recovery of thymopoiesis may improve outcomes after CBT.

Original languageEnglish (US)
Pages (from-to)4543-4551
Number of pages9
JournalBlood
Volume110
Issue number13
DOIs
StatePublished - Dec 15 2007

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Komanduri, K. V., St. John, L. S., De Lima, M., McMannis, J., Rosinski, S., McNiece, I., Bryan, S. G., Kaur, I., Martin, S., Wieder, E. D., Worth, L., Cooper, L. J. N., Petropoulos, D., Molldrem, J. J., Champlin, R. E., & Shpall, E. J. (2007). Delayed immune reconstitution after cord blood transplantation is characterized by impaired thymopoiesis and late memory T-cell skewing. Blood, 110(13), 4543-4551. https://doi.org/10.1182/blood-2007-05-092130