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 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.