Long-Lasting CD3 ⁺ T-Cell Deficiency after Cord Blood Stem Cell Transplantation in a Human Herpesvirus 6-Infected Child

Abstract

We report a long-lasting (8-month) reactivation of human herpesvirus 6 (HHV-6) infection in child who had undergone cord blood stem cell transplantation. The reactivation was characterized by high viral loads and by immediate-early mRNA positivity. HHV-6 infection was associated with a deep depletion of CD3, while the CD4/CD8 ratio remained substantially unchanged. CASE REPORTA 6-year-old male with relapsed acute lymphoblastic leukemia (ALL) and in second remission underwent transplantation of cord blood stem cells (CBSC) from his HLA-identical sister. The main clinical events observed during the patient's follow-up could be summarized as follows. On day ϩ12 after transplantation, a first-grade graft-versus-host disease was easily controlled by cortisone. At day ϩ15, the child suffered an acute febrile episode lasting 2 days, followed by a transient cytomegalovirus (CMV) infection from day ϩ20 to day ϩ23, documented by PP65 antigenemia and PCR positivity in blood samples and successfully treated with foscarnet. Finally, a hemorrhagic cystitis was retrospectively related to a simian virus 40 infection (3). The engraftment was complete with Ͼ500 polymorphonuclear leukocytes/l on day ϩ17. Currently, the child is alive and in good clinical condition.The virological follow-up started on day ϩ15 and lasted until day ϩ289. A set of virological investigations (to detect the presence of, i.e., CMV, Epstein-Barr virus, human herpesvirus 6 [HHV-6] and HHV-7, adenovirus, and polyomaviruses) was performed weekly. For this study, peripheral blood mononuclear cell (PBMC) dry pellets stored at Ϫ80°C were analyzed.

Immune cells subpopulations in cerebrospinal fluid and peripheral blood of patients with Aneurysmal Subarachnoid Hemorrhage

“…Additionally, PB CD4 + and CD8 + T cells were more activated compared with controls, assessed by CD69 expression. CD3 downregulation from the cell surface is normally associated with in vitro and in vivo T-cell activation (Comar et al, 2005 ; Sullivan and Coscoy, 2008 ). We also study the expression of T-cell co-stimulatory molecule CD28 on CD4 + and CD8 + T cells.…”

U94 of human herpesvirus 6 inhibits in vitro angiogenesis and lymphangiogenesis

“…Real-time PCR for HHV-6 DNA was performed as described in ref. 37, with the following set of primers/probe: HHV6 U94(ϩ) (5Ј-GAG CGC CCG ATA TTA AAT GGA T-3Ј); HHV6 U94(Ϫ) (5Ј-GCT TGA GCG TAC CAC TTT GCA-3Ј); HHV6 U94 PROBE (5Ј-FAM-CTG GAA TAA TAA AAC TGC CGT CCC CAC C-TAMRA-3Ј). The standard curve was generated by amplification of a plasmid containing the targeted HHV-6 sequences.…”

HHV-6 infection of tonsils and adenoids in children with hypertrophy and upper airway recurrent infections

“…Although in immunocompromised patients HHV-6 caused otitis media, encephalitis, hepatitis, atypical lymphocytosis and cardiomyopathies presenting as severe form and death, in healthy subjects HHV-6 reactivation is considered a rare event even if specific sequences of this virus are been detected in children suffering by undifferentiated febrile or infectious mononucleosislike syndrome [5][6][7].…”