T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec-10

Abstract

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.

Immune regulation by CD52-expressing CD4 T cells

“…2 Yet another T-cell regulator has recently gained prominence by a recent report in Nature Immunology of CD4 T cells expressing high levels of CD52. 3 CD52 is a short peptide of 12 amino acids in humans linked at its C-terminus to a glycosylphosphatidylinositol (GPI) anchor. Its single N-glycosylation site is occupied by large sialylated polylactossamine on a tetra-antennary fucosylated mannose core.…”

Lectin Galactoside-binding Soluble 3 Binding Protein (LGALS3BP) Is a Tumor-associated Immunomodulatory Ligand for CD33-related Siglecs

“…Therefore, it is possible that LGALS3BP could orchestrate the inhibition of different immune cells. Although Siglec-5 is expressed predominantly on myeloid cells such as neutrophils and monocytes/macrophages, Siglec-10 is also expressed on B cells (6,10), and recent evidence suggests that Siglec-10 acts with properly glycosylated CD52 to allow binding and inhibition of T cell activation (51). Moreover, Siglec-9 is expressed on a subpopulation of CD8 T cells (54).…”

Alemtuzumab for multiple sclerosis: the new concept of immunomodulation

“…Since it is highly negatively charged it has been supposed that its function consisted in hampering cell adhesion, thus allowing cells to freely move around (see the review of [23]). Although a recent study has found that activated CD4 T cells expressing high levels of CD52 may have regulatory activities on T effector lymphocytes [2] the function of CD52 remains partially unknown.…”