Abstract
Vγ9Vδ2 T cell responses in HIV‑exposed Uninfected (HEU) Infants
David Rach1, Hao-Ting Hsu2, Nginache Nampota3, Godfrey Mvula3, Felix A. Mkandawire3, Osward M. Nyirenda3, Bernadette Hritzo1, Ingrid Peterson4, Franklin R Toapanta4, Marcelo B Sztein4, Miriam Laufer4, Kirsten E. Lyke4, Cristiana Cairo2
1Molecular Microbiology and Immunology Graduate Program, University of Maryland School of Medicine, Baltimore, USA. 2Institute of Human Virology, University of Maryland School of Medicine, Baltimore, USA. 3Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi. 4Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, USA
Maternal antiretroviral therapy (ART) effectively prevents perinatal infection of infants born to HIV+ women. However, during the first six months of life HIV-exposed, uninfected (HEU) infants exhibit increased infectious morbidity compared to HIV unexposed (HU) infants. Dysfunction of the infant immune system, driven directly or indirectly by prenatal HIV/ART exposure, is thought to contribute to this outcome. Vγ9Vδ2 T (Vδ2) cells, with their ability to rapidly release Th1 cytokines and respond to IL-23, are likely to play a key role against pathogens in early life. Due to elevated inflammation at the fetal-maternal interface, Vδ2 cells, which are sensitive to inflammatory cytokines, may be dysfunctional in HEU infants. This issue, however, has not been investigated. We are analyzing a well-characterized Malawian infant cohort, comparing infants born to women with: A) ART-treated HIV infection, with undetectable viral load since before conception (HEU-lo); B) HIV infection diagnosed and treated at mid-gestation or later, with high viral load at enrollment (HEU-hi); C) no HIV infection (HU). We are employing conventional and spectral flow cytometry for a detailed assessment of cord blood Vδ2 cells.Ex vivo, we observed an increased frequency of Vδ2 cells in cord blood of HEU-hi infants compared to HU infants. Following short polyclonal stimulation, the frequency of Vδ2 cells producing IFNγ, or both INFγ and TNFα was only significantly elevated in HEU-lo infants. TCR-mediated restimulation of Vδ2 cells resulted in lower frequency of Th1 cytokine producing cells and CD107a+ cells in HEU-hi infants after expansion with BCG, but not after expansion with Zoledronate. Results for our Malawian neonates confirm elevated Vδ2 cell frequencies in the cord blood of HEU infants, which we previously observed in a Nigerian cohort.To optimize the use of precious clinical specimens and extend the analyses to the other human innate-like subsets, we designed a 29-color spectral flow cytometry panel that enables a comprehensive profiling of Vδ2 T, MAIT and NKT cells. The direct comparison of conventional and spectral data for Vδ2 cells will help validate the performance of large spectral flow cytometry panels to highlight the impact of HIV prenatal exposure on these rare subsets.
License
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