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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1406-1412.
Prepublished online as a Blood First Edition Paper on April 13, 2006; DOI 10.1182/blood-2005-11-012864.


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TRANSPLANTATION

Prospective simultaneous quantification of human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in young recipients of allogeneic hematopoietic stem cell transplants

Daniele Lilleri, Giuseppe Gerna, Chiara Fornara, Laura Lozza, Rita Maccario, and Franco Locatelli

From the Servizio di Virologia, Unità di Oncoematologia Pediatrica, and Laboratori Sperimentali di Ricerca, Area Trapiantologica, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.

We investigated immune reconstitution against human cytomegalovirus (HCMV) in 57 hematopoietic stem cell transplant (HSCT) recipients, aged 1 to 24 years, through a novel method combining T-cell stimulation by HCMV-infected autologous dendritic cells with simultaneous cytometric quantification of HCMV-specific, IFN{gamma}-producing CD4+ and CD8+ T cells. Lymphoproliferative response (LPR) to HCMV antigens was also determined. Patients were stratified into 2 groups according to HCMV serostatus, comprising 39 HCMV-seropositive (R+) and 18 HCMV-seronegative (R) patients who received a transplant from a sero-positive donor. Recovery of both HCMV-specific CD4+ and CD8+ T-cell immunity occurred in all 39 R+ patients within 6 months and in 6 (33%) of 18 R patients within 12 months. In R+ patients, the median numbers of HCMV-specific CD8+ and CD4+T cells were significantly higher than those of healthy controls, starting from days +60 and +180, respectively. In R– patients, the median numbers of HCMV-specific T cells were consistently lower than in R+ patients. LPR was delayed compared with reconstitution of IFN{gamma}-producing T cells. Patients with delayed specific immune reconstitution experienced recurrent episodes of HCMV infection. HCMV seropositivity of young HSCT recipients is the major factor responsible for HCMV-specific immune reconstitution, irrespective of donor serostatus, and measurement of HCMV-specific T cells appears useful for correct management of HCMV infection.


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