Abstract
Interleukin-2 (IL-2) has both pro- and anti-inflammatory properties that have been harnessed clinically and that are used experimentally to modulate leukocyte subsets in vivo. In mice, the bioavailability and half-life of IL-2 in vivo can be increased by complexing recombinant IL-2 with different clones of anti-IL-2 monoclonal antibodies that differentially target the cytokine to cells expressing different kinds of IL-2 receptors. While the impacts of systemic IL-2: anti-IL-2 antibody complex (IL-2C) administration are well-defined in the spleen and peripheral lymph nodes, how immune cells in the gut and gut-associated lymphoid tissues respond to IL-2C is not well characterized. Here, we analyze how major leukocyte populations in these tissues respond to IL-2C. We find that IL-2C targeting cells expressing IL-2 receptor beta cause an acute decrease in cellularity of Peyer’s Patches while cell numbers in the lamina propria and intraepithelial lymphocytes are unaffected. Cell contraction in Peyer’s Patches is associated with the apoptosis of multiple B cell subsets. Our results are important to consider for understanding off-target impacts of IL-2C regimes in experimental models and for considering how IL-2 may contribute to the etiology or severity of gut-associated conditions such as Crohn’s Disease.
Highlights
Interleukin-2 is a pleiotropic cytokine that regulates responses of diverse cell types both during homeostasis and immune responses[1,2]
We investigated the impacts of these IL-2 signals on the cellular composition of gut-associated lymphoid tissues (GALT) and compared them to changes observed in the spleen and peripheral lymph nodes in the same animals
The cellularity of the mesenteric lymph nodes (mLN) increased after IL-2 antibody complex (IL-2C) treatment (Fig. 1B) but treatment did not impact the total number of mLN present
Summary
Interleukin-2 is a pleiotropic cytokine that regulates responses of diverse cell types both during homeostasis and immune responses[1,2]. A better understanding of how IL-2 signals affect leukocyte populations in the gut and gut-associated lymphoid tissues (GALT) under steady state conditions may provide insight into how the cytokine can impact disease states To address these knowledge gaps, we treated naive mice with IL-2C containing 2 μg of recombinant IL-2 for 3 consecutive days by i.p. injection. We show that PP B cells recover within two weeks after cessation of IL-2C administration, indicating that the treatment does not permanently disrupt PP B cell homeostasis or the supporting PP architecture These results may have relevance to the understanding of how IL-2 can impact gastrointestinal diseases and should be taken into account when interpreting results of mouse models employing S4B6 IL-2C
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