Wednesday, July 27, 2016

Brain generates an autonomous immune protection against infection

Vaccines save lives. However even for most of vaccines that work we don't know why they work, i.e. we have no clue about protection correlates. They just work. Only source of information in human vaccine studies that are readily available is antibody titre analysis in serum [in blood]. But more recent studies in mice question the whole premise of vaccination strategy and analysis of its [correlates of] effectiveness. 

I am talking about tissue resident memory T cells. Several studies now clearly showed that most of the protection against infection is driven by local tissue-resident memory T cells rather than memory T cells found in circulation. For example, new study in Journal of Experimental Medicine showed that protection against brain viral infection is due to local brain tissue resident memory CD8 T cells, CD8 TRM cells.

To test the role of brain CD8 TRM cells in protection against viral infection the authors used recombinant, attenuated strain of LCMV virus (rLCMV). Initially they showed that unlike i.v. injection, when rLCMV  strain was administered directly in the brain (intrathecally) it led to robust development brain CD8 TRM cells.  

Moreover, when these mice were later challenged with WT virulent LCMV strain, mice with brain CD8 TRM cells showed superior control of virus (development of protective function of brain CD8 TRM cells were Ag-specific, IFN-γ and perforin-dependent, but CD4 and NK cell independent).

To further test the role of brain CD8 TRM cells in viral protection, the authors depleted circulating CD8 T cells with antibody. Still, these mice were fully protected against viral challenge with just brain CD8 TRM cells (Ab depletion does not affect tissue resident T cells). These data suggested that brain CD8 TRM cells were providing superior and independent protection against viral infection (though I don't think the authors have tested CD8 T cell depletion on mice injected with rLCMV intrathecally alone, because in most experiments on mice were done either with i.v. or i.v.+ injections).

In summary, This study supports idea that correlates of some of viral [vaccine] protections could be found in tissues rather than in the blood.

David Usharauli

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