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Preservation of lymphocyte functional fitness in perinatally-infected and treated HIV+ pediatric patients displaying sub-optimal viral control.
Khanolkar, Aaruni; Muller, William J; Simpson, Bridget M; Cerullo, Jillian; Williams, Ruth; Sowers, Sun Bae; Matthews, Kiana; Mercader, Sara; Hickman, Carole J; D'Aquila, Richard T; Liu, Guorong.
Afiliação
  • Khanolkar A; Department of Pathology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
  • Muller WJ; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
  • Simpson BM; Division of Infectious Diseases, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
  • Cerullo J; Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
  • Williams R; Department of Pathology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
  • Sowers SB; Department of Pathology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
  • Matthews K; Division of Infectious Diseases, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
  • Mercader S; Viral Vaccine Preventable Diseases Branch, Division of Viral Diseases, National Center for Immunization & Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA 30333, USA.
  • Hickman CJ; Viral Vaccine Preventable Diseases Branch, Division of Viral Diseases, National Center for Immunization & Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA 30333, USA.
  • D'Aquila RT; Viral Vaccine Preventable Diseases Branch, Division of Viral Diseases, National Center for Immunization & Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA 30333, USA.
  • Liu G; Viral Vaccine Preventable Diseases Branch, Division of Viral Diseases, National Center for Immunization & Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA 30333, USA.
Article em En | MEDLINE | ID: mdl-35434722
Background: Host-pathogen dynamics associated with HIV infection are quite distinct in children versus adults. We interrogated the functional fitness of the lymphocyte responses in two cohorts of perinatally infected HIV+ pediatric subjects with early anti-retroviral therapy (ART) initiation but divergent patterns of virologic control. We hypothesized that sub-optimal viral control would compromise immune functional fitness. Methods: The immune responses in the two HIV+ cohorts (n = 6 in each cohort) were benchmarked against the responses measured in age-range matched, uninfected healthy control subjects (n = 11) by utilizing tests for normality, and comparison [the Kruskal-Wallis test, and the two-tailed Mann-Whitney U test (where appropriate)]. Lymphocyte responses were examined by intra-cellular cytokine secretion, degranulation assays as well as phosflow. A subset of these data were further queried by an automated clustering algorithm. Finally, we evaluated the humoral immune responses to four childhood vaccines in all three cohorts. Results: We demonstrate that contrary to expectations pediatric HIV+ patients with sub-optimal viral control display no significant deficits in immune functional fitness. In fact, the patients that display better virologic control lack functional Gag-specific T cell responses and compared to healthy controls they display signaling deficits and an enrichment of mitogen-stimulated CD3 negative and positive lymphocyte clusters with suppressed cytokine production. Conclusions: These results highlight the immune resilience in HIV+ children on ART with sub-optimal viral control. With respect to HIV+ children on ART with better viral control, our data suggest that this cohort might potentially benefit from targeted interventions that might mitigate cell-mediated immune functional quiescence.

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article