Accelerated CD8+ T cell maturation in infants with perinatal HIV infection
Lesley R. de Armas,
Vinh Dinh,
Akshay Iyer,
Suresh Pallikkuth,
Rajendra Pahwa,
Nicola Cotugno,
Stefano Rinaldi,
Paolo Palma,
Paula Vaz,
Maria Grazia Lain,
Savita Pahwa
Affiliations
Lesley R. de Armas
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA
Vinh Dinh
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA
Akshay Iyer
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA
Suresh Pallikkuth
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA
Rajendra Pahwa
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA
Nicola Cotugno
Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; Chair of Pediatrics, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
Stefano Rinaldi
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA
Paolo Palma
Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; Chair of Pediatrics, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
Paula Vaz
Instituto Nacional de Saúde, Marracuene, Maputo Province, Mozambique
Maria Grazia Lain
Fundação Ariel Glaser contra o SIDA Pediátrico, Maputo, Mozambique
Savita Pahwa
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA; Corresponding author
Summary: In perinatal HIV infection, early antiretroviral therapy (ART) initiation is recommended but questions remain regarding infant immune responses to HIV and its impact on immune development. Using single cell transcriptional and phenotypic analysis we evaluated the T cell compartment at pre-ART initiation of infants with perinatally acquired HIV from Maputo, Mozambique (Towards AIDS Remission Approaches cohort). CD8+ T cell maturation subsets exhibited altered distribution in HIV exposed infected (HEI) infants relative to HIV exposed uninfected infants with reduced naive, increased effectors, higher frequencies of activated T cells, and lower frequencies of cells with markers of self-renewal. Additionally, a cluster of CD8+ T cells identified in HEI displayed gene profiles consistent with cytotoxic T lymphocytes and showed evidence for hyper expansion. Longitudinal phenotypic analysis revealed accelerated maturation of CD8+ T cells was maintained in HEI despite viral control. The results point to an HIV-directed immune response that is likely to influence reservoir establishment.
