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Expansion of Human Cytomegalovirus (HCMV) Immediate-Early 1-Specific CD8 + T Cells and Control of HCMV Replication after Allogeneic Stem Cell Transplantation
- Source :
- Journal of Virology. 82:10143-10152
- Publication Year :
- 2008
- Publisher :
- American Society for Microbiology, 2008.
-
Abstract
- Recovery of human cytomegalovirus (HCMV)-specific T immunity is critical for protection against HCMV disease in the early phase after allogeneic stem cell transplantation (SCT). Using an enzyme-linked immunospot assay with overlapping 15-mer peptides spanning pp65 and immediate-early 1 HCMV proteins, we investigated which HCMV-specific CD8 + gamma interferon-positive (IFN-γ + ) T-cell responses against pp65 and IE-1 were associated with control of HCMV replication in 48 recipients of unmanipulated HLA-matched allografts at 3 months (M3) and 6 months (M6) after SCT and in 23 donors. At M3 after SCT, the magnitude of the pp65-specific IFN-γ-producing CD8 + T-cell response was greater in recipients than in donors, regardless of HCMV status. In contrast, expansion of IE-1-specific CD8 + T cells at M3 was associated with protection against HCMV, and no patient with this expansion had HCMV replication at M3. At M6, the number of HCMV-specific CD8 + T cells against both pp65 and IE-1 had expanded in all recipients, regardless of their previous levels of HCMV replication. The recipients' HCMV-specific CD8 + T cells already detectable in related donors were predominantly targeting pp65. In contrast, in 40% of the cases, the HCMV-specific CD8 + T cells in recipients involved new CD8 + T-cell specificities undetectable in their related donors and preferentially targeting IE-1. Taken together, these results showed that the delay in reconstituting IE-1-specific CD8 + T cells is correlated with the lack of protection against HCMV in the first 3 months after SCT. They also show that IE-1 is a major antigenic determinant of the early restoration of protective immunity to HCMV after SCT.
- Subjects :
- Adult
Male
Human cytomegalovirus
Adolescent
viruses
Immunology
Cytomegalovirus
CD8-Positive T-Lymphocytes
Virus Replication
medicine.disease_cause
Microbiology
Immediate early protein
Herpesviridae
Immediate-Early Proteins
T-Lymphocyte Subsets
Betaherpesvirinae
Virology
medicine
Humans
Transplantation, Homologous
Cytotoxic T cell
Aged
Transplantation Chimera
biology
virus diseases
Cell Differentiation
Middle Aged
biochemical phenomena, metabolism, and nutrition
biology.organism_classification
medicine.disease
Transplantation
surgical procedures, operative
Insect Science
Cytomegalovirus Infections
Pathogenesis and Immunity
Female
Stem cell
CD8
Stem Cell Transplantation
Subjects
Details
- ISSN :
- 10985514 and 0022538X
- Volume :
- 82
- Database :
- OpenAIRE
- Journal :
- Journal of Virology
- Accession number :
- edsair.doi.dedup.....236c967f6b1a31bc9c04d7f833774d9d