CTLA-4–mediated transendocytosis of costimulatory molecules primarily targets migratory dendritic cells

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Science Immunology  31 May 2019:
Vol. 4, Issue 35, eaaw0902
DOI: 10.1126/sciimmunol.aaw0902

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  • RE: CTLA-4 mediated transendocytosis of co-stimulatory molecules primarily targets migratory dendritic cells
    • Dr Dianne Sika-Paotonu CQS MRSNZ, Associate Dean (Pacific)/Senior Lecturer Pathology & Molecular Medicine, Wellington School of Medicine & Health Sciences, University of Otago, New Zealand

    To the Editor,

    I read with very keen interest the article by Ovcinnikovs, V. R. et al. (1) and titled “CTLA-4 mediated transendocytosis of co-stimulatory molecules primarily targets migratory dendritic cells”.

    Although the cytotoxic T lymphocytes associated protein-4 (CTLA-4) has been identified as having a critical (negative) regulatory role for immunotherapeutic strategies and approaches, its contribution towards immune homeostasis is less well understood.

    CTLA-4 is found on T cells and is capable of capturing co-stimulatory molecules such as CD80 and CD86 via a process known as transendocytosis (TE). CTLA-4 uses this mechanism to control CD28 mediated co-stimulation of T cells.

    Previous work has demonstrated that T regs normally carry high levels of CTLA-4, and that without these high levels, irregularities in transendocytosis and T reg suppression activity are displayed.

    Overall, this work explored the role of CTLA-4 in maintaining immune homeostasis and showed that T regs outperformed T-cell populations at TE. Migratory Dendritic Cell (DC) populations were also identified as the main target for Treg based CTLA-4-dependent regulation under steady state conditions, within the in-vivo setting.

    The application of these findings to the infection and inflammatory setting, with consideration of the associated inflammatory stimuli will be important next steps.

    Overall an interesting set of detailed studies with important r...

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    Competing Interests: None declared.

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