Lymph Node Innate Lymphoid Cells (ILCs) in HIV Infected Children are Highly Activated Despite Sustained Depletion in Blood

Innate lymphoid cells (ILCs) are important for response to infection and immune development in early life. HIV infection in adults has a profound effect on ILCs, but the impact from birth is unknown. Here we studied vertically HIV infected children from birth, and found severe and persistent depletion of all circulating ILCs. In contrast to CD4 T-cells, circulating ILCs are not restored by long-term antiretroviral therapy, but could be rescued by treatment from birth. Remaining helper ILCs in blood were transcriptionally silent, whilst NK cells display limited regulation of genes associated with functional impairment, and CD4 T-cells show strong transcriptional activity. In stark contrast to blood, lymphoid (tonsil) tissue ILCs from infected children had a robust and coordinated transcriptional response to infection, while CD4 T-cell subsets were transcriptionally silent. These data suggest an important and on-going role for ILCs in lymphoid tissue of HIV infected children that requires further investigation.