Blood-circulating memory-phenotype CD4+ T cells rapidly accumulate in ischemic organs to exacerbate tissue injury in an innate manner

While previous studies revealed their innate immune function in infectious and autoimmune contexts, functional significance of MP cells in ischemia remains unclear. Ischemia-reperfusion injury (IRI) is induced by acute occlusion of organ-feeding arteries and subsequent reperfusion where innate immunity plays an important role.

Here we show that blood-circulating MP lymphocytes rapidly infiltrate to the gut in the absence of antigen recognition during intestinal IRI. This MP migration is directed by α4β7 that binds to vascular MAdCAM-1, with the latter expression immediately upregulated by ischemia-induced TNF-α. Moreover, gut-accumulating MP cells respond to IL-12 to produce IFN-γ in an innate manner to orchestrate neutrophils, thereby exacerbating tissue injury.