Cytomegalovirus-specific CD4+ and CD8+ T-cells follow a similar reconstitution pattern allogeneic stem cell transplantation

Aaron E. Foster, David J. Gottlieb, Mary Sartor, Mark S. Hertzberg, Kenneth F. Bradstock

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Cytomegalovirus (CMV) is a common herpes virus that can cause significant morbidity and mortality in immuno-compromised individuals, particularly those undergoing allogeneic stem cell transplantation (SCT) for hematological malignancies. Recent studies have examined the kinetics of CMV-specific CD8+ T-cell reconstitution after SCT transplantation and have found virus-specific cytotoxic T-lymphocyte regeneration to be dependent on CMV serologic status and CMV reactivation events. However, the reconstitution kinetics of CMV-specific CD4+ T-cells under these same circumstances were not addressed. In this study, we used HLA class I peptide tetramer for CMV pp65 and cytokine flow cytometry to follow the reconstitution of both CD4+ and CD8+ CMV-specific T-cells after allogeneic SCT. We found that following SCT in which both donors and recipients are CMV seropositive, virus-specific CD4+ T-helper cells show the same reconstitution kinetics as CD8+ cytotoxic T-cells. Following CMV reactivation, a synchronous but temporary increase in both CD4+ and CD8+ CMV-specific lymphocytes occurs. The pattern repeats itself after subsequent episodes of CMV reactivation. These data imply that both CD4+ and CD8+ lymphocytes are necessary for an efficient immune response to CMV and suggest that CD4+ and CD8+ CMV-specific T-cells are required for the complete restoration of CMV immunity. These findings may have important implications in the development of CMV-specific adoptive immunotherapy strategies.

Original languageEnglish (US)
Pages (from-to)501-511
Number of pages11
JournalBiology of Blood and Marrow Transplantation
Volume8
Issue number9
DOIs
StatePublished - 2002

Keywords

  • Allogeneic bone marrow transplantation
  • CMV reactivation
  • Cytokine flow cytometry
  • Cytotoxic T-lymphocyte

ASJC Scopus subject areas

  • Transplantation

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