Intestinal helminth infection induces highly functional resident memory CD4⁺ T cells in mice

Abstract

Immunity to intestinal nematodes requires CD4⁺ Th2‐cell responses, including IL‐4 and IL‐13 production. Chronic infection with intestinal nematodes leads to downregulation of these responses, and few functional T helper (Th) 2 cells are detected in secondary lymphoid organs in the chronic phase or after abrogation of infection. Here, we show with a natural murine infection with Heligmosomoides polygyrus that highly functional memory Th2 cells persist in the lamina propria and in addition in the peritoneal cavity (PC) after abrogation of infection. While both tissue‐resident memory (TRM) populations proliferate in situ and express IL‐4, IL‐5, and IL‐13 upon TCR‐dependent stimulation, only peritoneal memory cells express high levels of the IL‐33 receptor and produce IL‐5 and IL‐13 upon TCR‐independent stimulation with IL‐33 and IL‐7. Most importantly, PC‐derived TRM cells are able to mediate anti‐helminthic effects by decreasing the fecundity of female worms upon transfer into recipient mice. These results show that nonlymphoid compartments can serve as reservoirs for Th2 memory cells, and furthermore that innate effector function of Th2 memory cells is restricted to CD4⁺ memory T cells residing in the PC.

Intestinal helminth infection promotes IL-5- and CD4+ T cell-dependent immunity in the lung against migrating parasites

“…23 Furthermore, Hp itself has recently been shown to induce local memory CD4 + T cells that can be re-stimulated by IL-33 in a TCR-independent manner to release IL-5 and IL-13. 48 Building on these results, we show that IL-33 can stimulate IL-5 release from Hp-induced CD4 + T cells in the lung, which leads to the subsequent activation of eosinophils that can contribute to killing of migrating Nb larvae.…”

Th2/1 Hybrid Cells Occurring in Murine and Human Strongyloidiasis Share Effector Functions of Th1 Cells

“…Hence Th2/1 cells may be important to ensure that the helminth-infected host is able to quickly and adequately react to co-infections where an unabated IFN-γ response is crucial. Furthermore, IFN-γ production by Th2/1 cells generated during helminth infection often including tissue migratory larval stages may be advantageous in preventing bacterial dissemination facilitated by tissue damage (Pesce et al, 2008), especially upon parasite re-exposure of organs densely seeded with Th2 memory cells (Steinfelder et al, 2017). We currently assess if Th2/1 cells constitute a considerable source of IFN-γ and of other factors affecting the immune response to the parasite and, possibly, coinfecting pathogens.…”

CD4+ Memory T Cells at Home in the Tissue: Mechanisms for Health and Disease

“…Th1 TRMs generated in this model accumulate in the lamina propria and epithelium, and are maintained in an IL-15 independent manner. Th2 TRM cells can also be identified in the lamina propria and peritoneal cavity after infection with Heligmosomoides polygyrus ( 75 ). Re-challenge infection results in TCR dependent production of IL-4, IL-5, and IL-13, although TRM cells in the peritoneal cavity are additionally able to produce cytokines in response to IL-33 and IL-7 signals alone.…”