Increased Expression of sST2 in Early HIV Infected Patients Attenuated the IL-33 Induced T Cell Responses.

Abstract

T cell responses were less functional and persisted in an exhausted state in chronic HIV infection. Even in early phase of HIV infection, the dysfunction of HIV-specific T cells can be observed in rapid progressors, but the underlying mechanisms are not fully understood. Cytokines play a central role in regulating T cell function. In this study, we sought to elucidate whether IL-33/ST2 axis plays roles in the regulation of T cell function in HIV infection. We found that the level of IL-33 was upregulated in early HIV-infected patients compared with that in healthy controls and has a trend associated with disease progression. In vitro study shows that IL-33 promotes the expression of IFN-γ by Gag stimulated CD4+ and CD8+T cells from HIV-infected patients to a certain extent. However, soluble ST2 (sST2), a decoy receptor of IL-33, was also increased in early HIV infected patients, especially in those with progressive infection. We found that anti-ST2 antibodies attenuated the effect of IL-33 to CD4+ and CD8+T cells. Our data indicates that elevated expression of IL-33 in early HIV infection has the potential to enhance the function of T cells, but the upregulated sST2 weakens the activity of IL-33, which may indirectly contribute to the dysfunction of T cells and rapid disease progression. This data broadens the understanding of HIV pathogenesis and provides critical information for HIV intervention.

• Authors: Xian Wu, Yao Li, Cheng-Bo Song, Ya-Li Chen, Ya-Jing Fu, Yong-Jun Jiang, Hai-Bo Ding, Hong Shang, Zi-Ning Zhang
• Journal: Frontiers in immunology (Front Immunol) Vol. 9 Pg. 2850 ( 2018) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 30564243 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)

Chemical References

• IFNG protein, human
• IL1RL1 protein, human
• IL33 protein, human
• Interleukin-1 Receptor-Like 1 Protein
• Interleukin-33
• Interferon-gamma

Topics

• Adult
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Cells, Cultured
• Disease Progression
• HIV Infections (blood, immunology, virology)
• HIV-1 (immunology)
• Humans
• Interferon-gamma (immunology, metabolism)
• Interleukin-1 Receptor-Like 1 Protein (antagonists & inhibitors, immunology, metabolism)
• Interleukin-33 (antagonists & inhibitors, immunology, metabolism)
• Lymphocyte Activation
• Male
• Primary Cell Culture
• Sexual and Gender Minorities
• Up-Regulation (immunology)
• Young Adult