Human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in adult allogeneic hematopoietic stem cell transplant recipients and immune control of viral infection.

Abstract

BACKGROUND:

Human cytomegalovirus infection is the most frequent viral complication in patients undergoing hematopoietic stem cell transplantation. We investigated the development of human cytomegalovirus-specific T cells in adult recipients of hematopoietic stem cell transplants.

DESIGN AND METHODS:

From May 2003 through October 2006 a total of 45 patients were monitored for human cytomegalovirus-specific T-cell reconstitution. Human cytomegalovirus-infected autologous dendritic cells were used as a stimulus to detect interferon-gamma-producing human cytomegalovirus-specific CD8(+) and CD4(+) T cells during the first year after transplantation. Interleukin-2 production by specific T cells was also determined.

RESULTS:

Human cytomegalovirus infection was detected in the blood of 39/45 patients at a median of 29 days after transplantation. Human cytomegalovirus-specific T-cell reconstitution followed reactivation of latent human cytomegalovirus infection at a median time of about 2 months after transplantation. Only donor human cytomegalovirus-seronegativity and bone marrow as a stem cell source were found to delay specific T-cell reconstitution significantly. Levels of three CD8(+) and one CD4(+) human cytomegalovirus-specific T-cells/microL blood had a positive predictive value of around 80% for identifying patients able to control human cytomegalovirus infection spontaneously. Five patients who received high doses of steroids for treatment of graft-versus-host disease developed human cytomegalovirus infection requiring pre-emptive treatment despite high levels of interferon-gamma-producing T cells in response to human cytomegalovirus. Specific interleukin-2 production was not detected in patients with human cytomegalovirus infection requiring treatment, while 90% of patients who spontaneously controlled human cytomegalovirus infection had T cells that produced interleukin-2 and interferon-gamma.

CONCLUSIONS:

Pre-transplant human cytomegalovirus infection of the recipient is a major factor driving human cytomegalovirus-specific immune reconstitution. Control of human cytomegalovirus infection likely requires the presence of both interferon-gamma and interleukin-2 producing T cells. Corticosteroid treatment may favor active viral replication even in patients with specific T cells.

• Authors: Daniele Lilleri, Chiara Fornara, Antonella Chiesa, Daniela Caldera, Emilio Paolo Alessandrino, Giuseppe Gerna
• Journal: Haematologica (Haematologica) Vol. 93 Issue 2 Pg. 248-56 (Feb 2008) ISSN: 1592-8721 [Electronic] Italy
• PMID: 18245650 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IE1 protein, Human herpesvirus 1
• Immediate-Early Proteins
• Interleukin-2
• Phosphoproteins
• Viral Matrix Proteins
• cytomegalovirus matrix protein 65kDa
• Interferon-gamma

Topics

• Adult
• Aged
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cytomegalovirus (immunology)
• Cytomegalovirus Infections (immunology)
• Dendritic Cells (immunology, transplantation)
• Female
• Follow-Up Studies
• Graft vs Host Disease (immunology, prevention & control)
• Hematopoietic Stem Cell Transplantation
• Humans
• Immediate-Early Proteins (immunology)
• Immunity, Cellular
• Interferon-gamma (immunology)
• Interleukin-2 (immunology)
• Kinetics
• Male
• Middle Aged
• Phosphoproteins (immunology)
• Recovery of Function (immunology)
• Time Factors
• Transplantation, Autologous
• Transplantation, Homologous
• Viral Matrix Proteins (immunology)