Thursday, July 16, 2015

Foxp3+ Treg-derived IL-10 stabilizes anti-viral CD8 T cell memory formation

CD8 T cells can eliminate infected or tumor cells. Vaccine formulation that could improve CD8 T cell effector function and memory formation would be highly beneficial against intracellular infections such as HIV, TB, malaria or against tumors.

New study in Nature Immunology provided evidence that Foxp3+ Treg-derived IL-10 modulates CD8 Tcm memory formation.

Initially, the authors showed the proportion of central memory CD8 T cells (Tcm) generated after acute viral infection in IL-10KO mice were significantly reduced. No data are shown about actual Tcm numbers, though. No data are shown about actual viral titre or its clearance, either. Not cool.

Interestingly, presence of IL-10 was only relevant between day 8-15 post-infection (during CD8 T effector cell contraction phase). Here the authors have used PBS, rather than isotype antibody, as a control for anti-IL-10 antibody blockade. Not cool.

Next, the authors found that it was IL-10 derived from Foxp3+ Treg cells that influenced Tcm formation.

Conditional ablation of Foxp3+ Treg cells during early stages of infection had the same effect.

More importantly, viral antigen-specific CD8 memory T cells harvested from IL-10 fl/fl Foxp3-Cre mice (that selectively lacks IL-10 in Foxp3+ Tregs) showed reduced survival and reduced protection upon secondary antigen exposure in naive recipients.

Mechanistically, the authors hypothesized that hyper-inflammatory milieu found in IL-10 fl/fl Foxp3-Cre hosts at day 15 post viral infection could contribute to reduced Tcm formation. However, the authors did not try to actually test this hypothesis.

Finally, adoptive transfer of WT Foxp3+ Treg cells at day 8 post infection could rescue Tcm phenotype.

In summary, these results suggest that at some point (day 8-15) post viral infection Foxp3+ Treg-derived IL-10 reduces overall host's activation status and enables Tcm phenotype formation.

David Usharauli

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