Selectivity of bovine interleukin-2 mutein stimulation on bovine peripheral blood mononuclear cells

• Published in: Journal of Veterinary Medical Science Vol. 87; no. 7; pp. 781 - 790
• Main Authors: MITOMA, Shuya, UTO, Tomofumi, FUKAYA, Tomohiro, TOMINAGA, Moe, SEKIGUCHI, Satoshi, SATO, Katsuaki, NORIMINE, Junzo
• Format: Journal Article
• Language: English
• Published: Japan JAPANESE SOCIETY OF VETERINARY SCIENCE 2025; Japan Science and Technology Agency; The Japanese Society of Veterinary Science
• Subjects: Animals; bovine interleukin-2; Cancer therapies; Cattle; CD122; CD122 antigen; CD25 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - drug effects; CD8 antigen; Cell surface; Cytokines; Immunology; Interleukin 2; Interleukin-2 - genetics; Interleukin-2 - pharmacology; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Leukocytes (mononuclear); Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Lymphocytes; Lymphocytes T; mutein; natural killer cell; Natural killer cells; Peripheral blood mononuclear cells; selective stimulation; Signal transduction; bovine interleukin-2; mutein; selective stimulation; natural killer cell; CD122
• ISSN: 0916-7250; 1347-7439; 1347-7439
• DOI: 10.1292/jvms.24-0470

Delivery of engineered interleukin-2 (IL-2) variants (muteins) is thought to be a promising cancer therapy in humans and mice. Our previous study indicated that bovine IL-2 (boIL-2) has a great potential to elicit NK cell activity for which distribution of IL-2 receptors on the target cell surface influences signal transduction. We developed nine boIL-2 muteins and examined the influence of the muteins on bovine peripheral blood mononuclear cells in vitro. On bovine peripheral mononuclear cells, NK cells strongly expressed CD122, followed by CD8+ T cells, while CD4+ T cells and γδ T cells did not show significant CD122 expression. All boIL-2 muteins showed decreasing in binding to boIL-2 receptor α, CD25, while maintaining their ability to bind to boIL-2 receptor βγ, CD122/CD132, heterodimer. The mutein F44A and E63A suppressed CD4+ T cell expansion but maintained the NK cell expansion. These results indicate that boIL-2 muteins can alter immunological outcomes and may be used for clinical intervention for a disease progression.