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The two faces of IL-2: a key driver of CD8+ T-cell exhaustion

Cellular & Molecular Immunology volume 18, pages 1641–1643 (2021)Cite this article

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The body undergoes abnormal, pathological immune responses when antigens are present at too great an excess for the immune system to handle or the body is persistently exposed to antigens. The etiology of many types of chronic diseases is partially related to such conditions; thus, understanding the pathophysiological processes of these chronic diseases is of paramount importance for therapeutic purposes. A recent paper published in Nature Immunology revealed the unexpected involvement of the T cell-activating cytokine interleukin (IL)-2 in counteracting the immune attack on tumors, a finding that will provide new options for cancer therapy.1

Tissue parenchymal cells and stromal cells, including immune cells, rapidly produce proinflammatory mediators in response to an invading pathogen to initiate a series of innate immune responses linked to eliminating the pathogen. The inflammatory environment created early in this process also plays a major role in shaping T cell activation and differentiation, which orchestrate an adaptive immune response that protects against pathogens in cooperation with innate immunity. In many cases, the functions of proinflammatory mediators are not restricted to this immune-activating stage. These mediators also contribute to resolving the immune response by inducing the expression of immunomodulatory and tissue-repair molecules. This process is thought to be typical of negative feedback regulation. When the immune system confronts persistent exposure to antigens, as seen in chronic infections, tumors, and autoimmune diseases, uncontrolled inflammatory responses frequently create a potent negative feedback loop, resulting in the differentiation of “paralyzed” or immunosuppressive immune cells to an abnormal extent. Exhausted T (Tex) cells and myeloid-derived suppressor cells (MDSCs) represent these two respective categories of cells. The generation of these cells is believed to be an adaptation to detrimental and unrestrained immune responses.2 Although such an adaptation is effective in preventing a disastrous outcome, it is a tremendous obstacle to disease therapy.

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Fig. 1: IL-2 is essential for CD8+ T cell exhaustion within tumors.

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Acknowledgements

Byungsuk Kwon’s laboratory is supported by a grant from the University of Ulsan (2021-0404).

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  1. School of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea

    Byungsuk Kwon

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Kwon, B. The two faces of IL-2: a key driver of CD8+ T-cell exhaustion. Cell Mol Immunol 18, 1641–1643 (2021). https://doi.org/10.1038/s41423-021-00712-w

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