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

Abstract

Empirical data from survivors of Lassa fever and experimental disease modelling 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 responses 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 non-human primate model. Using an antibody-mediated T cell depletion strategy prior to and post-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 observed in the CD4-depleted group when compared to non-depleted 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 impact on the development of Lassa fever in non-human primates.