Thursday, December 31, 2015

IL-2 instructs allergen-specific tissue resident memory TH2 cell development

IL-2 is one of the first cytokines [interleukins] discovered and we still have no clear idea of the extent of its involvement and role within immune system. One reason has to do with the fact that IL-2 "in vitro" and IL-2 "in vivo" behave if completely 2 different cytokines.

So, if I see new paper that could tell us more about IL-2, I can't resist reading it. This week journal Immunity has published one such article. There, the authors showed that IL-2 signaling via its high-affinity receptor IL-2α (also known as CD25) directed development of allergen-specific tissue resident memory TH2 cells. I will discuss only those data that are relevant and unequivocal for the story.

For this study, the authors used class II tetramers and i.v. labeling techniques to identify and track house dust mite (HDM) allergen-specific tissue resident T cells. They showed that primary allergen exposure generates lung tissue resident HDM-specific tetramer-positive CD4 T cells.

These lung tissue resident tetramer-positive CD4 T cells expressed IL-13 upon HDM re-challenge (that identified them as TH2 cells).

Next, using parabiont mouse model the authors showed that tetramer-positive CD4 T cells found in allergen challenged lung tissue were bona fide non-circulatory resident-memory TH2 cells.

Finally, using WT:CD25KO mixed bone marrow chimera mice the authors showed that development of lung tissue resident memory TH2 cells required IL-2 signaling via its high-affinity receptor IL-2α.

In summary, this study suggests that IL-2 signaling via its high-affinity receptor IL-2α is mandatory for resident-memory TH2 cell development. This is addition to already known IL-2 roles in Foxp3+ Treg and memory CD8 T cell development. From therapeutic point of view, this is one big mess.

David Usharauli

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