Functional impairment and inflammatory changes of foxp3+ regulatory t cells in human acute viral infection = 급성 바이러스성 감염에서 조절 T 세포의 기능 부전 및 염증성 변화

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FoxP3+ regulatory T (Treg) cells play a major role in maintaining the immune homeostasis by preventing the activation of self-reactive T cells as well as in controlling a series of immune responses in viral infections. Treg cells, during chronic viral infections, have been shown to hamper virus-specific T cell immunity and thereby to allow persistence of viral infection. In contrast, roles of Treg cells in human acute viral infection remain largely unknown and functional changes of Treg cells in the context of immunopathology have not been reported so far. Herein, we investigated several functional changes of Treg cells and their potential implications in immunopathogenesis in acute hepatitis A (AHA). In the present study, we showed that overall in vitro suppressive activity of Treg cell population was compromised in AHA patients. Attenuation in suppressive activity was closely correlated with the severity of liver damage, indicating a protective role of Treg cells in immunopathogenesis of human acute viral infection. In addition, decreased Treg cell-mediated suppression in AHA could be attributed to reduced frequency of circulating Treg cells, which was also correlated with the degree of tissue damage. Assessment of immunophenotypes of Treg cells of AHA patients showed that they contained lower percentage of proliferating population and exhibit-ed increased susceptibility to apoptosis. In fact, spontaneous apoptosis of Treg cells were increased direct ex vivo, which might be a potential mechanism of contracted Treg cell pool size leading to enhanced immunopathology in AHA. We also investigated whether functional plasticity of Treg cells was responsible for the impaired function of Treg cells and tissue damage in patients with AHA. We examined the production of a variety of inflammatory cytokines from Treg cells in response to TCR stimulation. We found that a considerable proportion of Treg cells produced TNF-α following TCR stimulation in patients with AHA. I...
Shin, Eui-Cheolresearcher신의철
한국과학기술원 : 의과학대학원,
Issue Date
513944/325007  / 020085215

학위논문(박사) - 한국과학기술원 : 의과학대학원, 2013.2, [ viii, 90 p. ]


regulatory T cells; FoxP3; immunopathogenesis; plasticity; 조절 T 세포; FoxP3; 면역병리; 가변성; 바이러스 감염; viral infection

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