Memory T cells clear a persistent CNS infection in the absence of severe tissue injury

Tuesday, October 09, 2012 — Poster Session I
1:00 p.m. – 3:00 p.m	Natcher Conference Center, Building 45	NINDS	INFECTDIS-1

* FARE Award Winner

Authors

• J Herz
• D McGavern

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 clinics. Our laboratory models immunotherapy by transferring anti-viral memory T cells into mice persistently infected from birth with lymphocytic choriomeningitis virus. 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 monocytes). Memory T cells also enlist the support of nearly all brain resident myeloid cells (microglia) by converting them into CD11c-expressing antigen-presenting cells (APCs). Interestingly, we observed morphologically similar CD11c+ microglia in the brain of a virally infected human, suggesting that conversion of microglia into APCs is conserved across species. Notably, CD11c+ microglia were protected from T cell mediated apoptosis. We propose that successful non-cytopathic viral clearance from the brain by therapeutic T cells results from tailored chemokine production and conversion of resident myeloid cells into CD11c+ APCs that can then be engaged locally by anti-viral T cells.

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