T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec-10
- Author(s)
- Bandala-Sanchez, E; Zhang Y; Reinwald, S; Dromey, JA; Lee, BH; Qian, JY; Bohmer, RM; Harrison, LC;
- Details
- Publication Year 2013-07,Volume 14,Issue #7,Page 741-748
- Journal Title
- NATURE IMMUNOLOGY
- Publication Type
- Journal Article
- 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.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- MULTIPLE-SCLEROSIS; AUTOIMMUNE-DISEASE;
- Research Division(s)
- Molecular Medicine
- Publisher's Version
- https://doi.org/10.1038/ni.2610
- NHMRC Grants
- NHMRC/637301, NHMRC/516700,
- Terms of Use/Rights Notice
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Creation Date: 2013-07-01 12:00:00