Functionally diverse T cell populations interact to maintain homeostasis of the immune system. We found that human and mouse antigen-activated T cells with high expression of the lymphocyte surface marker CD52 suppressed other T cells. CD52(hi)CD4(+) T cells were distinct from CD4(+)CD25(+)Foxp3(+) regulatory T cells. Their suppression was mediated by soluble CD52 released by phospholipase C. Soluble CD52 bound to the inhibitory receptor Siglec-10 and impaired phosphorylation of the T cell receptor-associated kinases Lck and Zap70 and T cell activation. Humans with type 1 diabetes had a lower frequency and diminished function of CD52(hi)CD4(+) T cells responsive to the autoantigen GAD65. In diabetes-prone mice of the nonobese diabetic (NOD) strain, transfer of lymphocyte populations depleted of CD52(hi) cells resulted in a substantially accelerated onset of diabetes. Our studies identify a ligand-receptor mechanism of T cell regulation that may protect humans and mice from autoimmune disease.

Download full-text PDF

Source
http://dx.doi.org/10.1038/ni.2610DOI Listing

Publication Analysis

Top Keywords

soluble cd52
12
cell regulation
8
inhibitory receptor
8
receptor siglec-10
8
cd52hicd4+ cells
8
cells
6
cell
5
regulation mediated
4
mediated interaction
4
interaction soluble
4

Similar Publications

Background & Aims: Infectious complications determine the prognosis of cirrhosis patients. Their infection susceptibility relates to the development of immuneparesis, a complex interplay of different immunosuppressive cells and soluble factors. Mechanisms underlying the dynamics of immuneparesis of innate immunity remain inconclusive.

View Article and Find Full Text PDF

Soluble CD52 mediates immune suppression by human seminal fluid.

Front Immunol

December 2024

School of Biosciences and Bio21 Molecular Science and Biotechnology Institute, Faculty of Science, The University of Melbourne, Melbourne, VIC, Australia.

Seminal fluid provides for the carriage and nutrition of sperm, but also modulates immunity to prevent allo-rejection of sperm by the female. Immune suppression by seminal fluid has been associated with extracellular vesicles, originally termed prostasomes, which contain CD52, a glycosylated glycophosphoinositol-anchored peptide released from testicular epithelial cells. Previously, we reported that human T cell-derived CD52, bound to the danger-associated molecular pattern protein, high mobility group box 1 (HMGB1), suppresses T cell function via the inhibitory sialic acid-binding immunoglobulin-like lectin-10 (Siglec-10) receptor.

View Article and Find Full Text PDF
Article Synopsis
  • - The treatment options for non-Hodgkin lymphoma (NHL) have improved with the introduction of monoclonal antibody (MAB) therapy, particularly focusing on B cell and T cell subtypes, and categorized into aggressive and indolent forms.
  • - Rituximab, an anti-CD20 MAB, revolutionized treatment for indolent B cell NHL, like follicular lymphoma, by directly targeting cancerous B cells and becoming FDA approved in 1997.
  • - Despite its effectiveness, challenges such as resistance mechanisms have prompted interest in combining immunotherapy with radio-sensitizing agents, leading to advancements in drugs like 90Y-ibritumomab tiuxetan and ofatumumab
View Article and Find Full Text PDF

Previous studies suggest that short peptides from the heptad repeat 2 (HR2) domain of gp41 expressed on the cell surface are more potent inhibitors of HIV-1 entry than soluble analogs. However, their therapeutic potential has only been examined using lentiviral vectors. Here, we aimed to develop CRISPR/Cas9-based fusion inhibitory peptide knock-in (KI) technology for the generation and selection of HIV-1-resistant T cells.

View Article and Find Full Text PDF

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B cell dysregulation and breaks in tolerance that lead to the production of pathogenic autoantibodies. We performed single-cell RNA sequencing of B cells from healthy donors and individuals with SLE which revealed upregulated CD52 expression in SLE patients. We further demonstrate that SLE patients exhibit significantly increased levels of B cell surface CD52 expression and plasma soluble CD52, and levels of soluble CD52 positively correlate with measures of lupus disease activity.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!