Background T cell responses are regulated by co-stimulatory and inhibitory receptors along with T cell receptor- and cytokine-mediated signals. CD51, also known as alpha v integrin (ITGAV), is a transmembrane glycoprotein of the integrin family involved in cell adhesion, migration, tumorigenesis, and other cellular functions.1–7 However, the expression and function of CD51 in CD8 T cells during activation have not been previously examined. Therefore, this study aimed to investigate the expression and role of CD51 specifically in CD8 T cells.
Methods Analysis of RNA-sequencing data from exhausted CD8 T cells in mice with chronic lymphocytic choriomeningitis virus (LCMV) or B16F10 tumor models revealed high expression of Itgav (encoding CD51) in exhausted CD8 T cells from both mouse models. Itgav expression increased as CD8 T cells underwent terminal differentiation, similar to the expression pattern of Pdcd1. To assess CD51 expression during T cell activation, we stimulated total splenocytes with anti-CD3 antibodies. Additionally, we examined CD51 expression in exhausted CD8 T cells using four murine models: chronic LCMV infection, B16F10 melanoma, CT26 colon carcinoma, and acute graft-versus-host disease (GvHD). To investigate the role of CD51 in CD8 T cell activation, we employed CD51-blocking antibodies in in vitro activation and utilized CRISPR-mediated knockdown (KD) of CD51 in P14 CD8 T cells in vivo.
Results in vitro T cell activation revealed delayed but subsequent upregulation of CD51 expression during CD8 T cell division. Moreover, high CD51 expression was observed in exhausted CD8 T cells from cases of chronic LCMV infection, B16F10 melanoma, CT26 colon carcinoma, and acute GvHD. Furthermore, CD51 expression increased as the cells became more differentiated. CRISPR-mediated knockdown of CD51 resulted in decreased numbers of virus-specific CD8 T cells during LCMV infection, while maintaining granzyme B expression and cytokine production. Blockade of CD51 using antibodies significantly restrained T cell proliferation while preserving CD8 T cell activity.
Conclusions Our study demonstrates the upregulation of CD51 and its impact on CD8 T cell proliferation. Moreover, we identified that CD51-blocking antibodies effectively inhibit T cell activation. These findings highlight CD51 as a newly identified immunomodulatory protein with potential for enhancing the effectiveness of anticancer treatments in tumor models and mitigating immunopathological damage in autoimmune disorders and graft-versus-host diseases.
Acknowledgements This study was supported by a National Research Foundation of Korea (NRF) grant (S.J.I.) funded by the Korean government (MSIT) (RS-2023–00211426) and by a National Cancer Center Grant (NCC203186) (S.J.I.). This research was also supported by Korea Basic Science Institute (National Research Facilities and Equipment Center) grant funded by the Ministry of Education (2020R1A6C101A191).
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Ethics Approval All experiments were conducted in accordance with the Institutional Animal Care and Use Committee guidelines of Sungkyunkwan University School of Medicine.
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