Cutting Edge: Innate Lymphoid Cells Suppress Homeostatic T Cell Expansion in Neonatal Mice

Abstract

In adult mice, lymphopenia-induced proliferation (LIP) leads to T cell activation, memory differentiation, tissue destruction, and a loss of TCR diversity. Neonatal mice are lymphopenic within the first week of life. This enables some recent thymic emigrants to undergo LIP and convert into long-lived memory T cells. Surprisingly, however, most neonatal T cells do not undergo LIP. We therefore asked whether neonate-specific mechanisms prevent lymphopenia-driven T cell activation. In this study, we show that IL-7R–dependent innate lymphoid cells (ILCs) block LIP of CD8+ T cells in neonatal but not adult mice. Importantly, CD8+ T cell responses against a foreign Ag are not inhibited by neonatal ILCs. This ILC-based inhibition of LIP ensures the generation of a diverse naive T cell pool in lymphopenic neonates that is mandatory for the maintenance of T cell homeostasis and immunological self-tolerance later in life.

CXCR3high CD8+ T cells with naïve phenotype and high capacity for IFN‐γ production are generated during homeostatic T‐cell proliferation

“…Consequently, the proportions of CXCR3 + cells in the NP CD8 + T‐cell population showed two distinct phases of increase at the neonatal and aged stages (Fig. A, right), corresponding to the physiological increase in T‐cell HP . Sorted CXCR3 + NP CD8 + T cells from neonatal and aged mice showed comparable functional features with an increased capacity for rapid IFN‐γ and TNFα production following PMA/ionomycin stimulation compared to the corresponding CXCR3 – counterparts, although the capacities were lower than in the corresponding CM CD8 + T cells (Fig.…”

IL-15 sustains IL-7R-independent ILC2 and ILC3 development

“…36). To perform this experiment, we first generated Rag1 −/− Il7ra −/− mice, as Il7ra −/− mice develop some T cells37 that may compete with ILCs for trophic factors38. We infected cohoused Rag1 −/− , Rag1 −/− Il7ra −/− and Rag2 −/− Il2rg −/− with a lethal dose of C. rodentium and measured weight loss and survival (Fig.…”

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells

“…102 In addition, ILC3 prevent spontaneous CD8 + T-cell activation in neonatal lymph nodes, although it remains unclear whether modulation of CD8 + T-cell responses is also dependent upon ILC3 antigen-presenting function or cell-cell interactions. 103 In addition to cell-to-cell interactions with adaptive immune cells, ILC3 have the capacity to modulate adaptive immune responses by the release of soluble mediators in the local tissue microenvironment. In this regard both gut NKp46 + and LTi-like ILC3 are an important source of granulocyte-macrophage colony stimulating factor (GM-CSF) under steady-state conditions.…”