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Journal of Virology, October 2008, p. 10143-10152, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.00688-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Expansion of Human Cytomegalovirus (HCMV) Immediate-Early 1-Specific CD8⁺ T Cells and Control of HCMV Replication after Allogeneic Stem Cell Transplantation

Laboratoire d'Immunologie Cellulaire et Tissulaire, INSERM U543, AP-HP, Université Pierre et Marie Curie-Paris6, Paris, France,¹ Service d'Hématologie Clinique, Hôpital Pitié-Salpêtrière, AP-HP, Université Pierre et Marie Curie-Paris6, Paris, France,² Laboratoire de Virologie, EA 2387, Université Pierre et Marie Curie-Paris6, Paris, France³

Received 27 March 2008/ Accepted 28 July 2008

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-⁺) 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--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.

Published ahead of print on 6 August 2008.