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Human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in adult allogeneic hematopoietic stem cell transplant recipients and immune control of viral infection.
Haematologica. 2008 Feb; 93(2):248-56.H

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+Show Affiliations

Servizio di Virologia, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18245650

Citation

Lilleri, Daniele, et al. "Human Cytomegalovirus-specific CD4+ and CD8+ T-cell Reconstitution in Adult Allogeneic Hematopoietic Stem Cell Transplant Recipients and Immune Control of Viral Infection." Haematologica, vol. 93, no. 2, 2008, pp. 248-56.
Lilleri D, Fornara C, Chiesa A, et al. Human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in adult allogeneic hematopoietic stem cell transplant recipients and immune control of viral infection. Haematologica. 2008;93(2):248-56.
Lilleri, D., Fornara, C., Chiesa, A., Caldera, D., Alessandrino, E. P., & Gerna, G. (2008). Human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in adult allogeneic hematopoietic stem cell transplant recipients and immune control of viral infection. Haematologica, 93(2), 248-56. https://doi.org/10.3324/haematol.11912
Lilleri D, et al. Human Cytomegalovirus-specific CD4+ and CD8+ T-cell Reconstitution in Adult Allogeneic Hematopoietic Stem Cell Transplant Recipients and Immune Control of Viral Infection. Haematologica. 2008;93(2):248-56. PubMed PMID: 18245650.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in adult allogeneic hematopoietic stem cell transplant recipients and immune control of viral infection. AU - Lilleri,Daniele, AU - Fornara,Chiara, AU - Chiesa,Antonella, AU - Caldera,Daniela, AU - Alessandrino,Emilio Paolo, AU - Gerna,Giuseppe, PY - 2008/2/5/pubmed PY - 2008/4/2/medline PY - 2008/2/5/entrez SP - 248 EP - 56 JF - Haematologica JO - Haematologica VL - 93 IS - 2 N2 - 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. SN - 1592-8721 UR - https://www.unboundmedicine.com/medline/citation/18245650/Human_cytomegalovirus_specific_CD4+_and_CD8+_T_cell_reconstitution_in_adult_allogeneic_hematopoietic_stem_cell_transplant_recipients_and_immune_control_of_viral_infection_ L2 - https://doi.org/10.3324/haematol.11912 DB - PRIME DP - Unbound Medicine ER -