Author: Warner, Bryce M; Safronetz, David; Stein, Derek R
Title: Current research for a vaccine against Lassa hemorrhagic fever virus Document date: 2018_8_14
ID: 3zduon0f_6
Snippet: Several lines of evidence point to a strong T-cell response to LASV as critical for protection against LF. Defective T-cell responses predominate during severe LASV infection, while strong T-cell responses are typically seen in individuals who can control the infection. In NHP models, undetectable T-cell responses correlate with lethality. In these models, we see decreased proliferation, activation, cytokine production, as well as a lack of T-cel.....
Document: Several lines of evidence point to a strong T-cell response to LASV as critical for protection against LF. Defective T-cell responses predominate during severe LASV infection, while strong T-cell responses are typically seen in individuals who can control the infection. In NHP models, undetectable T-cell responses correlate with lethality. In these models, we see decreased proliferation, activation, cytokine production, as well as a lack of T-cell expression of CD25 and CD69, promoting disease progression. 13, 28 As already discussed, the lack of T-cell activation is likely due to an inhibition of the interaction between infected and antigen-primed DCs presenting LASV peptides to T cells. Indeed, LASV-infected DCs are unable to activate CD4 and CD8 T cells in vitro, while DCs infected with MOPV readily activate these cells. 27 The exact mechanisms of T-cell depletion are not clear; however, the ability of LASV to prevent DC activation likely plays a role. There is also evidence that LASV-specific T cells can contribute to disease through macrophage activation, resulting in deleterious cell-mediated inflammatory reactions and damage to secondary lymphoid organs. 29 The role this might play in active suppression of T-cell responses during LASV infection is unclear. This suggests that, while likely important for protection against disease, strong T-cell responses may contribute to pathogenesis and this should be examined further in more appropriate models.
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