title: Quantitative and qualitative CD4 T cell immune responses related to adenovirus DNAemia in hematopoietic stem cell transplantation.
abstract: The nature of adenovirus (AdV)-specific T cells that could best predict the capacity of immunocompromised host to fight AdV is unclear. To this aim, 47 pediatric patients were enrolled for at least 3 months either at allogeneic bone marrow transplantation (BMT) (23 genoidentical, 18 unrelated of which 9 were 10/10 and 9 were 9/10 HLA-matched) or at unrelated cord blood transplantation (n = 6). Enumeration of AdV-specific CD4 T cells secreting cytokines (flow cytometry) and proliferative responses to AdV ((3)HT-incorporation) were compared to AdV-DNAemia. A total of 44/47 patients did not evidence AdV-DNAemia. Thirty-two of 44 (73%) developed CD4-mediated interferon-gamma (IFN-γ) responses to AdV (median 0.36 CD4/μL of blood) since the first month post-HSCT (n = 11: 8 genoidentical and 3 unrelated) or the third month (n = 21 additional patients). At 3 months, both incidence and level intensities of AdV-specific CD4 appeared similar in genoidentical and unrelated BMT (70% and 80%; 0.36 and 0.21 CD4/μL, respectively) and not statistically different from age-matched controls (76%; 1.35 CD4/μL), whereas cord blood transplanted patients exhibited similar incidence but higher level intensities (67%; 1.49 CD4/μL). Polyfunctional (IL2 + IFN-γ) and proliferative responses appeared later, after the third month. Three of 4 9/10 HLA-matched unrelated HSCT that did not develop immunity to AdV presented chemotherapy-resistant AdV-DNAemia at 3 to 5 months post-hematopoietic stem cell transplantation (HSCT). Two were successfully treated with AdV-specific CTL infusion. Monitoring, since month 1 post-HSCT, of IFN-γ-secreting AdV-specific CD4 appears suitable for early detection of at-risk patients especially in 9/10 HLA-matched unrelated HSCT and preferable to monitoring of more delayed IL2- and proliferative responses.
authors.affiliation: Laboratory of Immunology, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris, University Paris VII, 48 Boulevard Sérurier, Paris, France. valerie.guerin@rdb.aphp.fr
authors.forename: Valérie
authors.initials: V
authors.lastname: Guérin-El Khourouj
authors.forename: Jean-Hugues
authors.initials: JH
authors.lastname: Dalle
authors.forename: Béatrice
authors.initials: B
authors.lastname: Pédron
authors.forename: Karima
authors.initials: K
authors.lastname: Yakouben
authors.forename: Danièle
authors.initials: D
authors.lastname: Bensoussan
authors.forename: Débora Jorge
authors.initials: DJ
authors.lastname: Cordeiro
authors.forename: Lucas
authors.initials: L
authors.lastname: Peltier
authors.forename: Marie
authors.initials: M
authors.lastname: Ouachée-Chardin
authors.forename: André
authors.initials: A
authors.lastname: Baruchel
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Sterkers
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000257:Adenoviridae Infections / Q000097:blood / Q000276:immunology / Q000628:therapy; D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D004279:DNA, Viral / Q000097:blood* / Q000276:immunology; D005260:Female; D006402:Hematologic Diseases / Q000097:blood / Q000276:immunology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D007376:Interleukin-2 / Q000097:blood / Q000276:immunology; D008297:Male; D012189:Retrospective Studies; D014184:Transplantation, Homologous
chemical_list: D004279:DNA, Viral; C508594:IL2 protein, human; D007376:Interleukin-2; D007371:Interferon-gamma