CD4⁺ and CD8⁺ T cells are not the main driver of Lassa fever pathogenesis in macaques

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Abstract

Empirical data from survivors of Lassa fever and experimental disease modeling efforts, particularly those using mouse models, are at odds with respect to T cell–mediated pathogenesis. In mice, T cells have been shown to be imperative in disease progression and lethality, whereas in humans, an early and robust T cell response has been associated with survival. Here, we assessed the role of CD4+ and CD8+ T cells on disease progression and severity of Lassa virus infection in a nonhuman primate model. Using an antibody-mediated T cell depletion strategy prior to and after inoculation, we were able to examine Lassa virus infection in the absence of specific T cell responses. In animals depleted for either CD4+ or CD8+ T cells, Lassa virus infection remained uniformly lethal, with only a slight delay in disease progression was observed in the CD4-depleted group when compared with nondepleted controls. Milder pulmonary pathology was noticed in the absence of CD4+ or CD8+ T cells. Overall, our findings suggest that T cells have a limited effect on the development of Lassa fever in nonhuman primates.

Authors

Jérémie Prévost, Nikesh Tailor, Geoff Soule, Jonathan Audet, Yvon Deschambault, Robert Vendramelli, Jessica Prado-Smith, Kevin Tierney, Kimberly Azaransky, Darwyn Kobasa, Chad S. Clancy, Heinz Feldmann, Kyle Rosenke, David Safronetz