[T cell-mediated protective effect in cytomegalovirus infected murine astrocytes]
Hong Zhen1, Feng Fang, Yu-feng Zhou
1Pediatric Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. zhenhongzh@hotmail.com
Aim:
To explore T cell-mediated restriction of cytomegalovirus (CMV) in murine astrocytes.
Methods:
A T cell-astrocyte coculture system was established, in which astrocytes were infected with mouse cytomegalovirus. Proliferation of T cells was observed under inverted microscope and detected after CFSE staining by flow cytometry. ELISA was used to detect the levels of IFN-gamma and TNF-gamma in coculture supernatants. Observation of astrocyte cytopathic effect (CPE) and PCR assay of cytomegalovirus DNA were also performed.
Results:
After coculture for 3 d, T cells proliferation was observed under inverted microscope, and flow cytometry assay showed (6.68+/-0.61)% T cells had proliferated (P<0.01 compared with uninfected control). The level of IFN-gamma was (22.9+/-3.4) ng/L in coculture supernatants (P<0.05 compared with uninfected control). While levels of TNF-gamma were under 8 ng/L in both cytomegalovirus infected and uninfected groups. After coculture with T cells 31.25%-75% astrocyte CPE was diminished, and -75% cytomegalovirus DNA load was reduced. Cell-free coculture supernatants also exerted suppressive effect on CPE and viral DNA load. However, the antiviral effect of T cells diminished when added to fresh cytomegalovirus infected astrocytes, accompanied with the decreased level of T cells proliferation and IFN-gamma in coculture supernatants, suggesting the inhibition of T cells' function.
Conclusion:
Cytomegalovirus infected astrocytes could stimulate T cells proliferation and activation. Activated T cells had antiviral effect, which was partly mediated by soluble factors. The function of T cells was rapidly inhibited after activation, of which the underlying complicated mechanisms remain unclear and need further study.
Insights
Activated T cells restrict cytomegalovirus (CMV) in astrocytes, partly via soluble factors. However, T cell antiviral function rapidly declines, requiring further investigation into underlying mechanisms.
Area of Science:
- Immunology
- Virology
- Neuroscience
Context:
- Murine astrocytes are susceptible to cytomegalovirus (CMV) infection.
- T cell-mediated immunity plays a crucial role in controlling viral infections.
- The interaction between T cells and infected astrocytes in the central nervous system is not fully understood.
Purpose:
- To investigate the role of T cells in restricting CMV infection in murine astrocytes.
- To elucidate the mechanisms by which T cells exert antiviral effects on infected astrocytes.
- To examine the dynamics of T cell activation and function in response to CMV-infected astrocytes.
Summary:
- Coculture of T cells with CMV-infected murine astrocytes induced T cell proliferation and IFN-gamma production.
- Activated T cells demonstrated an antiviral effect, reducing astrocyte cytopathic effect and viral DNA load.
- Soluble factors released by activated T cells partially mediated the antiviral response.
- T cell antiviral function diminished rapidly post-activation, suggesting inhibitory mechanisms.
Impact:
- This study reveals a T cell-mediated antiviral response against CMV in astrocytes.
- Identifies soluble factors as contributors to the antiviral effect.
- Highlights the rapid inhibition of T cell function, opening avenues for future research on regulatory mechanisms in neuroinflammation and viral control.
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