New expression of PD-L1 on activated CD4+ T cells opens up new opportunities for cell interactions and signaling

Hum Immunol. 2024 Jul;85(4):110831. doi: 10.1016/j.humimm.2024.110831. Epub 2024 Jun 12.

Abstract

Surface expression of programmed death-ligand 1 (PD-L1) is mainly observed on antigen presenting cells (APC) such as monocytes or dendritic cells (DCs). Our results showing a high expression of PD-L1 on human naïve CD4+ effector T-cells (TEFFs) and CD4+ regulatory T cells (TREGs) after activation with human DCs, allow us to propose a new role for PD-L1 and its ligands and their potential impact on new signaling pathways. Indeed, expression of PD-L1 on activated CD4+T cells could allow cis interaction with its ligands such as PD-1 and CD80, thus disrupting interactions with other signaling receptors, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) or CD28, which interact with CD80. The ability to compete with hypothetical configuration modifications that may cause a change in affinity/avidity for the trans and cis interactions between these proteins expressed on T cells and/or DCs is discussed. As the study of cancer is strongly influenced by the role of the PD-L1/PD-1 pathway and CD4+T cells, new interactions, cis and/or trans, between TEFFs, TREGs and tumor cells are also proposed. The presence of PD-L1 on activated CD4+ T cells could influence the quality of the cytotoxic T lymphocyte response during priming to provide other help signals.

Keywords: CD4(+)T cells; Cancer; Human; Interaction; PD-L1.

Publication types

  • Review

MeSH terms

  • B7-1 Antigen / immunology
  • B7-1 Antigen / metabolism
  • B7-H1 Antigen* / immunology
  • B7-H1 Antigen* / metabolism
  • CD28 Antigens / immunology
  • CD28 Antigens / metabolism
  • CD4-Positive T-Lymphocytes* / immunology
  • CD4-Positive T-Lymphocytes* / metabolism
  • CTLA-4 Antigen / metabolism
  • Cell Communication* / immunology
  • Dendritic Cells* / immunology
  • Dendritic Cells* / metabolism
  • Humans
  • Lymphocyte Activation* / immunology
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Programmed Cell Death 1 Receptor* / metabolism
  • Signal Transduction*
  • T-Lymphocytes, Regulatory / immunology

Substances

  • B7-H1 Antigen
  • Programmed Cell Death 1 Receptor
  • CD274 protein, human
  • B7-1 Antigen
  • CTLA-4 Antigen
  • CD28 Antigens
  • PDCD1 protein, human
  • CTLA4 protein, human