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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{triangledown}

Karim Sacre,1 Stéphanie Nguyen,1,2 Claire Deback,3 Guislaine Carcelain,1 Jean-Paul Vernant,2 Véronique Leblond,2 Brigitte Autran,1* and Nathalie Dhedin1,2

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-{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.

* Corresponding author. Mailing address: Laboratoire d'Immunologie Cellulaire et Tissulaire, INSERM U543, Hôpital Pitié-Salpêtrière, 83 Bld de l'Hôpital, 75651 Paris Cedex 13, France. Phone: 33-1-42-17-74-81. Fax: 33-1-42-17-74-90. E-mail: brigitte.autran{at}psl.aphp-paris.fr

{triangledown} Published ahead of print on 6 August 2008.

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.





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