Interleukin-2 (IL2), a cytokine, exerts crucial functions in immune homeostasis. It impacts regulatory T (Treg) cells, and fine-tunes effector lymphocyte responses. IL2 was first identified as a growth factor for activated human T cell populations. Its signaling pathways regulate CD4+ T cell differentiation and function, as well as the effector and memory responses of CD8+ T cells. Dysregulation of IL2 or its responsiveness is associated with exhausted phenotypes in chronic viral infections and tumor responses [2].

Low-dose recombinant IL-2 has been used for Treg cell-based immunosuppressive strategies against immune pathologies, while high-dose IL-2 has shown success in stimulating anti-tumor immune responses [1]. In a mouse model of chikungunya virus-induced arthritis, treatment with an IL2/anti-IL2 complex increased both Tregs and effector (Teff) T cells, without significantly reducing inflammation. However, the anti-IL2 monoclonal antibody alone, which moderately increased IL2 levels and activated Tregs, decreased the average disease score. This suggests that the complex stimulates both Tregs and Teffs, while the antibody can shift the immune environment towards a tolerogenic state [3,4]. Mathematical models have been developed to study the impact of IL2 modulation therapies on T cell dynamics, simulating the effects of treatments like injection of IL2, anti-IL2 antibodies, IL2/anti-IL2 immune-complexes, and mutant variants of IL2. These models help determine the dose and timing conditions for potentiating either immunity or tolerance [5].

In conclusion, IL2 plays a dual-acting role in both immune activation and regulation. Studies using mouse models, such as those for chikungunya-induced arthritis and through mathematical models, have provided insights into its functions. These findings are valuable for understanding its role in immune-related diseases and for developing more effective IL2-based therapies for autoimmune diseases and cancer [1,2,3,4,5].

References:

1. Arenas-Ramirez, Natalia, Woytschak, Janine, Boyman, Onur. 2015. Interleukin-2: Biology, Design and Application. In Trends in immunology, 36, 763-777. doi:10.1016/j.it.2015.10.003. https://pubmed.ncbi.nlm.nih.gov/26572555/

2. Spolski, Rosanne, Li, Peng, Leonard, Warren J. . Biology and regulation of IL-2: from molecular mechanisms to human therapy. In Nature reviews. Immunology, 18, 648-659. doi:10.1038/s41577-018-0046-y. https://pubmed.ncbi.nlm.nih.gov/30089912/

3. Tritsch, Sarah R, Porzucek, Abigail J, Schwartz, Arnold M, Mores, Christopher N, Chang, Aileen Y. 2023. Effects of IL2/anti-IL2 antibody complex on chikungunya virus-induced arthritis in a mouse model. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.01.30.526329. https://pubmed.ncbi.nlm.nih.gov/36778306/

4. Tritsch, Sarah R, Porzucek, Abigail J, Schwartz, Arnold M, Mores, Christopher N, Chang, Aileen Y. 2023. Effects of rIL2/anti-IL2 antibody complex on chikungunya virus-induced chronic arthritis in a mouse model. In Scientific reports, 13, 7307. doi:10.1038/s41598-023-34578-x. https://pubmed.ncbi.nlm.nih.gov/37147383/

5. León, Kalet, García-Martínez, Karina, Carmenate, Tania. 2013. Mathematical Models of the Impact of IL2 Modulation Therapies on T Cell Dynamics. In Frontiers in immunology, 4, 439. doi:10.3389/fimmu.2013.00439. https://pubmed.ncbi.nlm.nih.gov/24376444/