Expansion of human cytomegalovirus (HCMV) immediate-early 1-specific CD8+ T cells and control of HCMV replication after allogeneic stem cell transplantation.
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-gamma(+)) 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-gamma-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.
Sacre
Karim
K
Laboratoire d'Immunologie Cellulaire et Tissulaire, INSERM U543, Hôpital Pitié-Salpêtrière, 83 Bld de l'Hôpital, 75651 Paris Cedex 13, France.
Nguyen
Stéphanie
S
Deback
Claire
C
Carcelain
Guislaine
G
Vernant
Jean-Paul
JP
Leblond
Véronique
V
Autran
Brigitte
B
Dhedin
Nathalie
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002454:Cell Differentiation; D003587:Cytomegalovirus / Q000276:immunology* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000276:immunology*; D014779:Virus Replication
D017874:Immediate-Early Proteins