Abstract
Calcium influx is critical for T cell effector function and fate. T cells are activated when T cell receptors (TCRs) engage peptides presented by antigen-presenting cells (APC), causing an increase of intracellular calcium (Ca2+) concentration. Co-receptors stabilize interactions between the TCR and its ligand, the peptide-major histocompatibility complex (pMHC), and enhance Ca2+ signaling and T cell activation. Conversely, some co-receptors can dampen Ca2+ signaling and inhibit T cell activation. Immune checkpoint therapies block inhibitory co-receptors, such as cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), to increase T cell Ca2+ signaling and promote T cell survival. Similar to CTLA-4 and PD-1, the co-receptor CD5 has been known to act as a negative regulator of T cell activation and to alter Ca2+ signaling and T cell function. Though much is known about the role of CD5 in B cells, recent research has expanded our understanding of CD5 function in T cells. Here we review these recent findings and discuss how our improved understanding of CD5 Ca2+ signaling regulation could be useful for basic and clinical research.
Highlights
T cells are a critical component of the adaptive immune system
T cell responses are influenced by signals that modulate the effects of the T cell receptor (TCR) and peptide-major histocompatibility complex interaction and initiate the transcription of genes involved in cytokine production, proliferation, and differentiation [1,2,3]
The TCR engages the peptide-major histocompatibility complex (pMHC) leading to tyrosine phosphorylation of CD3 and initiation of the Ca2+/Calcineurin/Nuclear factor of activated T cells (NFAT) or Protein kinase C-theta (PKCθ)/Nuclear factor-κ-light chain enhancer of activated B cells (NF-κB) or Mitogen-activated protein kinase (MAP kinase)/AP-1 pathways [4,5,6]
Summary
T cell responses are influenced by signals that modulate the effects of the T cell receptor (TCR) and peptide-major histocompatibility complex (pMHC) interaction and initiate the transcription of genes involved in cytokine production, proliferation, and differentiation [1,2,3]. Cell surface costimulatory molecules, such as co-receptor CD28, amplify TCR-pMHC complex signals and promote stronger intracellular interactions to prevent T cell anergy [7,8]. Cytokines such as interleukin-12 (IL-12), interferon α (INFα), and interleukin-1 (IL-1) promote T cell proliferation, differentiation, and effector functions [6]. We will consider CD5 Ca2+ signaling regulation in T cells and its potential physiological impact on immunometabolism, cell differentiation, homeostasis, and behavior
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