Abnormal lipid rafts related ganglioside expression and signaling in T lymphocytes in immune thrombocytopenia patients

Abstract

Aberrant T lymphocytes signaling is considered to play a crucial role in the abnormal immune state of primary immune thrombocytopenia (ITP). Lipid raft has been verified to engage in the T cell receptor (TCR)-mediated T lymphocytes signal transduction. Whether lipid raft-associated T cells signal transduction has impact on the pathogenesis of ITP is still unconfirmed. In this study, we aimed to reveal the abnormality in structure and function of lipid rafts (LRs) in CD4⁺ and CD8⁺ T lymphocytes of patients with ITP. Our results showed that there was an increased lipid raft aggregation in ITP patients, while this kind of increase would not be influenced by platelet counts or therapeutic regimes. Stimulation by anti-CD3/CD28 monoclonal antibodies promoted enhanced lipid raft clustering in T lymphocytes of ITP patients compared with negative controls. Methyl-β-cyclodextrin (MβCD) could block the abnormal lipid raft aggregation and disrupt the TCR-mediated T cells proliferation and cytokines secretion, including both proinflammatory cytokines and anti-inflammatory cytokines. The spontaneous activation of T lymphocytes from ITP patients might be due to the elevated co-localization of protein tyrosine phosphatase (PTP) CD45 and lipid rafts in patients’ CD4⁺ and CD8⁺ T lymphocytes. These findings suggest that the autoactivation of T lymphocytes from ITP patients may lead to the abnormality in lipid raft structure and raft-anchored proteins, and the changes conversely promote the TCR-mediated T cells activation of ITP patients.

• Aggregation
• CD45
• lipid raft
• primary immune thrombocytopenia
• T lymphocytes

Acknowledgements

The authors would like to thank Dr Hao Zhang for assistance with the statistical analysis and Mrs. Mei Zhang for assistance with the figures.

Declaration of interest

We declare that we have no conflict of interest. None of the authors has any potential financial conflict of interest related to this manuscript. No other people or organizations that could influence (bias) the author’s work. No scientific writing assistance has been involved in this article. This work was supported in part by grants of National Natural Science Foundation of China (81070397, 81270581 and 81300385), Specialized Research Fund for the Doctoral Program of Higher Education (20131106120039) and Tianjin Municipal Science and Technology Commission (14JCZDJC35100 and 12JCQNJC08000).