MHCII-Mediated Dialog between Group 2 Innate Lymphoid Cells and CD4+ T Cells Potentiates Type 2 Immunity and Promotes Parasitic Helminth Expulsion

Abstract

SummaryGroup 2 innate lymphoid cells (ILC2s) release interleukin-13 (IL-13) during protective immunity to helminth infection and detrimentally during allergy and asthma. Using two mouse models to deplete ILC2s in vivo, we demonstrate that T helper 2 (Th2) cell responses are impaired in the absence of ILC2s. We show that MHCII-expressing ILC2s interact with antigen-specific T cells to instigate a dialog in which IL-2 production from T cells promotes ILC2 proliferation and IL-13 production. Deletion of MHCII renders IL-13-expressing ILC2s incapable of efficiently inducing Nippostrongylus brasiliensis expulsion. Thus, during transition to adaptive T cell-mediated immunity, the ILC2 and T cell crosstalk contributes to their mutual maintenance, expansion and cytokine production. This interaction appears to augment dendritic-cell-induced T cell activation and identifies a previously unappreciated pathway in the regulation of type-2 immunity.

Innate Lymphoid Cells in Type 2 Immune Responses

“…We, and others, recently confirmed that antigendriven CD4 ? T cell-derived IL-2 directly induces ILC2 proliferation and cytokine production in co-cultures (Mirchandani et al 2014;Oliphant et al 2014). Most interestingly, in these in vitro experiments, it was shown that ILC2 could directly affect CD4 ?…”

“…Thus, co-transfer of ILC2 markedly enhanced ovalbumin-specific T cell responses in the lungs of recipient mice (Mirchandani et al 2014). Furthermore, depletion of ILC2 diminishes adaptive Th2 responses to inhaled allergens (Gold et al 2014;Halim et al 2014) and parasites (Oliphant et al 2014). It is likely that ILC2 promote CD4 ?…”

“…T cell activation via MHC II-dependent peptide presentation. Importantly ILC2 express both MHC class II molecules and co-stimulatory ligands (Oliphant et al 2014) and are, thus, capable of providing both ''signal 1'' and ''signal 2'' required for the activation of naïve T cells. Of note, ILC2 appear to preferentially induce Th2 and oppose Th1 polarization of naïve T cells in a contact-dependent manner (Mirchandani et al 2014); however, the molecular mechanisms behind this effect are yet to be fully elucidated.…”

“…In this regard, following intranasal papain delivery, ILC2-derived IL-13 indirectly enhances T cell priming by promoting dendritic cell migration to draining lymph nodes . By contrast MHC class II-deficient ILC2 are incapable of restoring Th2 responses in N. brasiliensis-infected ILC2-depleted mice, indicating an important role for direct Agpresentation by ILC2 in vivo (Oliphant et al 2014). …”

“…A prior impediment to studying ILC2 function in vivo was the lack of animal models specifically lacking this cell type. However, recently described mouse strains allowing inducible deletion of ILC2 should allow the physiological roles of these populations in vivo to be fully dissected Oliphant et al 2014). Further important questions concern the function of ILC2 in human immunity and disease.…”