Impact of Neonatal Exposure to Malaria and HIV on the Frequency, Phenotype, and Function of __ T Cell Subsets at Birth
The Vδ2+ subset of γδ T cells possess intrinsic reactivity to malaria antigens and may be an important antimalarial effector mechanism, but there is evidence that chronic exposure to malaria and HIV is associated with the loss and dysfunction of this subset. It is unclear whether in utero exposure to malaria or HIV is associated with reduced frequencies and/or dysfunction of Vδ 2+ T cells. Leveraging cord blood samples to be collected as part of two parallel, NIH-funded randomized controlled trials of enhanced antimalarial chemoprevention given during pregnancy in HIV-infected and uninfected women, we will test the central hypothesis that in utero exposure to HIV or malaria results in loss and dysfunction of Vδ 2 γδ T cells. To determine the impact of in utero exposure to malaria, we will compare Vδ 2 frequencies, phenotype, and function between cord blood samples obtained from mothers given enhanced vs. standard of care antimalarial chemoprevention; to determine the impact of in utero exposure to HIV, we will compare Vδ 2 frequencies, phenotype, and function between cord blood samples obtained from HIV-infected vs uninfected mothers (both given enhanced antimalarial chemoprevention). Analyses will be performed using fresh cord blood mononuclear cells, and differences between groups will be compared using the Mann Whitney U test. Results from these studies should significantly advance our understanding of the mechanisms of protective immunity to malaria, and assist with the design of vaccines and other immunomodulatory interventions for malaria.