Memory T cells convert tissue resident myeloid cells into APCs during clearance of a persistent viral infection (166.28)

Abstract

Abstract Persistent viral infections are often very difficult to treat in humans. Adoptive immunotherapy is an approach that involves administration of anti-viral T cells and has shown some promise in the clinic. Our laboratory models adoptive immunotherapy by transferring anti-viral memory T cells into mice persistently infected from birth with lymphocytic choriomeningitis virus (LCMV). Here, we demonstrate that memory T cells can completely purge the brain of persistently infected mice without causing immunopathology or blood brain barrier breakdown. Memory T cells accomplish this by inducing a tailored release of chemoattractants that recruit adaptive immune cells, but few pathogenic innate immune cells (e.g. neutrophils and inflammatory monocytes) into the nervous system. Memory T cells also enlist the support of nearly all brain resident myeloid cells (referred to as microglia) by converting them into CD11c-expressing antigen-presenting cells (APCs). Following conversion, CD11c+ microglia release CCL5 and promote interactions with therapeutic memory T cells in the brain parenchyma. Our two photon imaging studies revealed that anti-viral CD8 T cells are more likely than CD4 T cells to decelerate and form stable interactions with brain-resident APCs. We propose that non-cytopathic viral clearance from the brain by therapeutic memory T cells results from tailored chemoattractant production and conversion of resident myeloid cells into CD11c+ APCs.