Molecular characterization and functional analysis of the leukocyte surface protein CD31 (original) (raw)
Related papers
Blood, 1995
CD31 (PECAM-1) is an immunoglobulin gene superfamily cell adhesion molecule found on vascular endothelium, platelets, and leukocytes. Lymphocyte expression of CD31 is most closely associated with the CD45RA+CD8+ naive T phenotype. CD31 has recently been shown to play a role in leukocyte egress to inflammatory sites. The mechanism of CD31 adhesion remains under investigation. Several investigators have reported evidence for a heterotypic ligand. We have previously shown that CD31 is phosphorylated with cell activation, which suggests a possible role for CD31 in cell activation events. We therefore studied the effects of CD31 antibodies on in vitro assays of lymphocyte activation. One CD31 antibody, LYP21, inhibited the mixed lymphocyte reaction (MLR) in a specific and dose-dependent fashion. An LYP21 epitope was localized to the sixth Ig domain of CD31. This peptide and a scrambled control peptide were synthesized and used to study effects of this epitope on lymphocyte activation. Th...
An immunologist's guide to CD31 function in T-cells
Journal of Cell Science, 2013
Although it is expressed by all leukocytes, including T-, B-lymphocytes and dendritic cells, the immunoglobulin-like receptor CD31 is generally regarded by immunologists as a marker of endothelial cell lineage that lacks an established functional role in adaptive immunity. This perception has recently been challenged by studies that reveal a key role for this molecule in the regulation of T-cell homeostasis, effector function and trafficking. The complexity of the biological functions of CD31 results from the integration of its adhesive and signaling functions in both the immune and vascular systems. Signaling by means of CD31 is induced by homophilic engagement during the interactions of immune cells and is mediated by phosphatase recruitment or activation through immunoreceptor tyrosine inhibitory motifs (ITIMs) that are located in its cytoplasmic tail. Loss of CD31 function is associated with excessive immunoreactivity and susceptibility to cytotoxic killing. Here, we discuss recent findings that have brought to light a non-redundant, complex role for this molecule in the regulation of T-cell-mediated immune responses, with large impact on our understanding of immunity in health and disease.
Role of CD31 Binding Partners in Viable Leukocyte Detachment from Macrophages
2007
Brown my supervisor, for endless support, encouragement and positivity especially through the dark times. Professor John Savill, for giving a Geordie girl a chance to prove herself. Dr Elisabeth Vernon-Wilson for teaching me the mysteries of molecular biology, and for generating site-directed mutagenesis vectors. Dr Jason King for assistance with siRNA constructs. Dr Cheryl Hunter for help with the lentivirus system.
2010
CD31 is an Ig-like molecule expressed by leukocytes and endothelial cells with an established role in the regulation of leukocyte trafficking. Despite genetic deletion of CD31 being associated with exacerbation of T cell-mediated autoimmunity, the contribution of this molecule to T-cell responses is largely unknown. Here we report that tumor and allograft rejection are significantly enhanced in CD31-deficient mice, which are also resistant to tolerance induction. We propose that these effects are dependent on an as yet unrecognized role for CD31-mediated homophilic interactions between T cells and antigen-presenting cells (APCs) during priming. We show that loss of CD31 interactions leads to enhanced primary clonal expansion, increased killing capacity, and diminished regulatory functions by T cells. Immunomodulation by CD31 signals correlates with a partial inhibition of proximal T-cell receptor (TCR) signaling, specifically Zap-70 phosphorylation. However, CD31-deficient mice do not develop autoimmunity due to increased T-cell death following activation, and we show that CD31 triggering induces Erkmediated prosurvival activity in T cells either in conjunction with TCR signaling or autonomously. We conclude that CD31 functions as a nonredundant comodulator of T-cell responses, which specializes in sizing the ensuing immune response by setting the threshold for Tcell activation and tolerance, while preventing memory T-cell death.
CD31 Acts as a Checkpoint Molecule and Is Modulated by FcγR-Mediated Signaling in Monocytes
Journal of Immunology, 2019
Monocytes and macrophages express FcgR that engage IgG immune complexes such as Ab-opsonized pathogens or cancer cells to destroy them by various mechanisms, including phagocytosis. FcgR-mediated phagocytosis is regulated by the concerted actions of activating FcgR and inhibitory receptors, such as FcgRIIb and SIRPa. In this study, we report that another ITIM-containing receptor, PECAM1/CD31, regulates FcgR function and is itself regulated by FcgR activation. First, quantitative RT-PCR and flow cytometry analyses revealed that human monocyte FcgR activation leads to a significant downregulation of CD31 expression, both at the message level and at surface expression, mainly mediated through FcgRIIa. Interestingly, the kinetics of downregulation between the two varied, with surface expression reducing earlier than the message. Experiments to analyze the mechanism behind this discrepancy revealed that the loss of surface expression was because of internalization, which depended predominantly on the PI3 kinase pathway and was independent of FcgR internalization. Finally, functional analyses showed that the downregulation of CD31 expression in monocytes by small interfering RNA enhanced FcgR-mediated phagocytic ability but have little effect on cytokine production. Together, these results suggest that CD31 acts as a checkpoint receptor that could be targeted to enhance FcgR functions in Ab-mediated therapies.
Engagement of CD30 shapes the secretion of cytokines by human γ δ T cells
European Journal of Immunology, 2000
CD30 is a member of the TNF receptor superfamily, previously shown to be expressed on Hodgkin's lymphoma cells and on normal activated lymphocytes. We here show that CD30 is highly expressed on recently activated human +ˇT cells. Elevated surface levels of this molecule persisted in long-term cultures of +ˇcells, without further cell stimulation. CD30 acted as a co-stimulus in +ˇT cells by potentiating the intracellular Ca 2+ fluxes induced by CD3 cross-linking. The engagement of CD30 enhanced the expression of several cytokines induced upon CD3 stimulation such as IL-4 and IFN-+ but not IL-10. The CC chemokines RANTES and macrophage inflammatory protein-1 g were constitutively expressed and not affected by stimulation. The inducible expression of the neutrophil chemoattractant IL-8 was enhanced by CD30 co-stimulation, as well as that of the CC chemokines I-309 and MDC, whereas the secretion of the monocyte chemotactic protein-1 was not detected. Triggering of CD30 may therefore modulate the expression of several cytokines released by +ˇcells; the expression of its physiologic ligand by APC and neutrophils at the site of infection may contribute to determine the outcome of an immune response.
Engagement of CD30 shapes the secretion of cytokines by human ??d T cells
Eur J Immunol, 2000
CD30 is a member of the TNF receptor superfamily, previously shown to be expressed on Hodgkin's lymphoma cells and on normal activated lymphocytes. We here show that CD30 is highly expressed on recently activated human +ˇT cells. Elevated surface levels of this molecule persisted in long-term cultures of +ˇcells, without further cell stimulation. CD30 acted as a co-stimulus in +ˇT cells by potentiating the intracellular Ca 2+ fluxes induced by CD3 cross-linking. The engagement of CD30 enhanced the expression of several cytokines induced upon CD3 stimulation such as IL-4 and IFN-+ but not IL-10. The CC chemokines RANTES and macrophage inflammatory protein-1 g were constitutively expressed and not affected by stimulation. The inducible expression of the neutrophil chemoattractant IL-8 was enhanced by CD30 co-stimulation, as well as that of the CC chemokines I-309 and MDC, whereas the secretion of the monocyte chemotactic protein-1 was not detected. Triggering of CD30 may therefore modulate the expression of several cytokines released by +ˇcells; the expression of its physiologic ligand by APC and neutrophils at the site of infection may contribute to determine the outcome of an immune response.
CD31 Exhibits Multiple Roles in Regulating T Lymphocyte Trafficking In Vivo
The Journal of Immunology, 2012
The role of CD31, an Ig-like molecule expressed by leukocytes and endothelial cells (ECs), in the regulation of T lymphocyte trafficking remains contentious. Using CD31-deficient mice, we show that CD31 regulates both constitutive and inflammation-induced T cell migration in vivo. Specifically, T cell:EC interactions mediated by CD31 molecules are required for efficient localization of naive T lymphocytes to secondary lymphoid tissue and constitutive recirculation of primed T cells to nonlymphoid tissues. In inflammatory conditions, T cell:EC CD31-mediated interactions facilitate T cell recruitment to Ag-rich sites. However, endothelial CD31 also provides a gate-keeping mechanism to limit the rate of Ag-driven T cell extravasation. This event contributes to the formation of Ag-specific effector T cell infiltrates and is induced by recognition of Ag on the endothelium. In this context, CD31 engagement is required for restoring endothelial continuity, which is temporarily lost upon MH...
Cellular Immunology, 1990
IL-2 production by PHA-stimulated MOLT 14 cells (a TcR y/&bearing human leukemic T cell line) and MOLT I6 cells (a TcR cY/fl-bearing human leukemic T cell line) was markedly augmented by coculturing with BALL-I cells (a human leukemic B cell line), or with recombinant human interleukin-lol (rhIL-lol). We have previously shown that the augmentation of IL-2 production, induced by BALL-1 cells, requires cell to cell contact and is an ILl independent pathway. In this report, the expression of the CD28 molecule on MOLT 14 cells and MOLT 16 cells was examined for its role in IL-2 production augmented by BALL-l cells. A I-hr preincubation of MOLT 14 cells and MOLT 16 cells with anti-CD28 mAb resulted in the inhibition of BALL-1 cell-induced augmentation of IL-2 production (90 and 62% inhibition of control, respectively). The inhibition was observed in a dose-dependent manner of anti-CD28 mAb added and reached a plateau level at concentrations of 0.05 &ml of anti-CD28 mAb. This was sufficient to cover all the CD28 molecules expressed on the surface of both T cells as detected by flow cytometric analysis. Flow cytometric analysis also showed that the inhibition was not due to a modulation ofCD28 molecules. In contrast, the treatment with anti-CD28 mAb did not inhibit IL-2 production which was augmented by rhIL-1 (Y costimulator. These results suggest that the CD28 molecule on the T cells is important for the interaction with BALL-l cells which causes the augmentation of IL-2 production and further imply that the CD28 molecule is a receptor for an accessory signal provided by BALL-I cells. D 1990 Academic PXS, hc.