Monday, September 15, 2014

Atavistic memory CD8 T cells

The second paper I am going to review about tissue resident memory T cells comes from David Masopust's lab

The results in this paper (1) are so straightforward and simple and sometimes confusing that it should have been published in Journal of Immunology rather than in journal Science.

To begin with, the authors are mentioning abbreviation FRT, however, I was unable to find what it stands for.

In this study, the authors transferred naive OT-I or P14 CD8 T cells into recipients infected one day later with VV-OVA or LCMV.

60 days later, tissue resident CD8 T cells were re-activated with locally deposited cognate gp33 peptide. This led to IFN-gamma dependent VCAM-1 up-regulation on local endothelial cells and VCAM-1 dependent recruitment of non-specific OT-I cells 

or B cells.

To test the biological significance of this observation, the authors established tissue resident pool of P14 CD8 memory T cells and then infected these mice with unrelated VV-OVA in presence or absence of cognate gp33 peptide. The authors found that re-activation of local gp33-specific P14 memory T cells greatly improved VV-OVA control, in contrast to VV-OVA challenge only, or when IFN-gamma, TNF-alpha, IL-2Rbeta were neutralized.

In sum, the authors concluded that local activation of local tissue resident memory CD8 T cells with cognate peptide facilitates control of unrelated viral infection through activation of innate cells (NK, DCs) and probably priming of naive T cells specific for challenged virus.

Now, these results are little bit confusing. First, it is not clear how initial i.v. viral infection establishes local tissue resident CD8 T cells in cervix. Second, it is not clear either how exactly local activation of tissue resident memory CD8 T cells of one specificity “helps” control unrelated virus. Third, if this “help” is antigen non-specific, any type of innate cells may be able to do the same upon viral infection. What is the advantage of memory CD8 T cells in this regard?


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