Prospective simultaneous quantification of human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in young recipients of allogeneic hematopoietic stem cell transplants.
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, IFNgamma-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 IFNgamma-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.
Lilleri
Daniele
D
Servizio di Virologia, Instituto di Ricovero e Cura a Carattere Scientifico San Matteo, 27100 Pavia, Italy.
Gerna
Giuseppe
G
Fornara
Chiara
C
Lozza
Laura
L
Maccario
Rita
R
Locatelli
Franco
F
D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D020127:Recovery of Function / Q000276:immunology*; D013997:Time Factors; D014184:Transplantation, Homologous
D007371:Interferon-gamma