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Numerical and functional defects in CD8 + CD28 - T-suppressor lymphocytes from patients with primary immune thrombocytopenia.
- Source :
-
British journal of haematology [Br J Haematol] 2017 Jul; Vol. 178 (2), pp. 292-301. Date of Electronic Publication: 2017 May 03. - Publication Year :
- 2017
-
Abstract
- Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder, and loss of immune tolerance has been implicated in ITP pathogenesis. CD8 <superscript>+</superscript> CD28 <superscript>-</superscript> suppressor (Ts) cells have an immunosuppression function and are involved in several autoimmune disorders. However, the role of Ts cells in ITP is currently not clear. Here, flow cytometry was used to detect the CD8 <superscript>+</superscript> CD28 <superscript>-</superscript> CD127 <superscript>-</superscript> proportion, which was decreased in active ITP patients compared with that of controls. Function analysis showed that immunosuppression of CD8 <superscript>+</superscript> CD28 <superscript>-</superscript> Ts cells in ITP patients was impaired. Mechanistic studies have shown that CD8 <superscript>+</superscript> CD28 <superscript>-</superscript> Ts cells from controls can downregulate CD80 and upregulate LILRB4 (ITL3) and LILRB2 (ILT4) expression on CD14 <superscript>+</superscript> monocytes, whereas these abilities were not found in Ts cells from ITP patients. Furthermore, Inducible T-cell costimulatory (ICOS) expression on the Ts cell surface after activation was decreased whereas programmed death 1 and interleukin 10 expression was not changed in ITP patients compared with those of controls. In summary, the down-regulated quantity and function of Ts cells in active patients indicated that a Ts defect was involved in ITP. Moreover, decreased ICOS expression and the loss of the ability to regulate co-stimulator expression on antigen-presenting cells partly explained the defective Ts-mediated suppression.<br /> (© 2017 John Wiley & Sons Ltd.)
- Subjects :
- Adolescent
Adult
Aged
Cytokines metabolism
Female
Humans
Immune Tolerance physiology
Inducible T-Cell Co-Stimulator Protein metabolism
Interferon-gamma biosynthesis
Interleukin-10 physiology
Lymphocyte Subsets physiology
Male
Middle Aged
Programmed Cell Death 1 Receptor metabolism
Transforming Growth Factor beta1 metabolism
Young Adult
CD28 Antigens metabolism
CD8-Positive T-Lymphocytes physiology
Purpura, Thrombocytopenic, Idiopathic immunology
T-Lymphocytes, Regulatory physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2141
- Volume :
- 178
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- British journal of haematology
- Publication Type :
- Academic Journal
- Accession number :
- 28466476
- Full Text :
- https://doi.org/10.1111/bjh.14661