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

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.