CD58 Immunobiology at a Glance.

Yalu Zhang,Qiaofei Liu,Quan Liao,Sen Yang

doi:10.3389/fimmu.2021.705260

Abstract

The glycoprotein CD58, also known as lymphocyte-function antigen 3 (LFA-3), is a costimulatory receptor distributed on a broad range of human tissue cells. Its natural ligand CD2 is primarily expressed on the surface of T/NK cells. The CD2-CD58 interaction is an important component of the immunological synapse (IS) that induces activation and proliferation of T/NK cells and triggers a series of intracellular signaling in T/NK cells and target cells, respectively, in addition to promoting cell adhesion and recognition. Furthermore, a soluble form of CD58 (sCD58) is also present in cellular supernatant in vitro and in local tissues in vivo. The sCD58 is involved in T/NK cell-mediated immune responses as an immunosuppressive factor by affecting CD2-CD58 interaction. Altered accumulation of sCD58 may lead to immunosuppression of T/NK cells in the tumor microenvironment, allowing sCD58 as a novel immunotherapeutic target. Recently, the crucial roles of costimulatory molecule CD58 in immunomodulation seem to be reattracting the interests of investigators. In particular, the CD2-CD58 interaction is involved in the regulation of antiviral responses, inflammatory responses in autoimmune diseases, immune rejection of transplantation, and immune evasion of tumor cells. In this review, we provide a comprehensive summary of CD58 immunobiology.

Highlights

Intercellular adhesion is vital for a range of immunological responses, including the interaction between T lymphocytes and target cells
At a study of the mechanism that NK-mediated cytotoxicity to breast cancer targets, unexpectedly, anti-CD58 mAb failed to inhibit NK-mediated killing but instead mediated the enhanced cytotoxicity associated with CD58 expression, albeit CD2 blockade mildly reduced cytotoxicity [145]. These results indicate NK-mediated cell lysis of breast cancer is potentiated through antibody-dependent cellular cytotoxicity (ADCC) against CD58
Regarding the roles of CD58 in tumor immunology, a looming but promising picture begins to come into sight from current studies (Table 1)

Summary

Introduction

Intercellular adhesion is vital for a range of immunological responses, including the interaction between T lymphocytes and target cells. In murine T cell hybridomas expressing human CD2, anti-CD59 mAbs suppress CD2mediated T cell activation, indicating that direct interaction of CD2 with CD59 likewise facilitates T cell-specific immune responses [84]. As an important secondary signal of T cell activation in response to CD58-positive antigen-bearing stimulator cells, CD2-CD58 signaling induces IL-2 secretion through influencing nuclear factor (NF)-mediated the transcription of the IL-2 promoterenhancer [121, 122], which maintains autocrine T cell growth and the generation of IFN and TNF [123].

Results

Conclusion