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Understanding and Enhancing Cytotoxic T Lymphocytes Function for Anti-Viral Immunity
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posted on 05.04.2017by Yew Ann Leong
such as those caused by chronic human immunodeficiency virus (HIV) hepatitis B
virus (HBV), and Epstein-Barr virus (EBV), are global epidemics that lead to
life-long diseases and impose significant health burdens. Cytotoxic T
lymphocytes (CTLs) are a population of adaptive immune cells specialized in
cytolysis of infected cells. However, CTLs fail to eliminate chronic infections
in majority of cases. There are several mechanisms by which these viruses evade
eradication by CTLs. One of the mechanisms commonly used by both HIV and EBV is
to 'hide' inside B cell follicles in secondary lymphoid organs which contain
fewer CTLs. Another strategy is to induce the exhaustion of T cells, a
phenomenon which significantly reduces the CTL’s capability to eliminate viral
infections. This thesis aims to tackle the chronic infections from these two
angles. The thesis consists of two parts. In the first part, I describe a novel
population of CTLs that are able to migrate into B cell follicles and control
infections therein. In the second part, I characterised a novel monoclonal
antibody that potentiates the bioactivity of an immunostimulatory cytokine,
interleukin-21 (IL-21), which boosted the number and cytotoxicity of CTLs.
Enhancing the follicular entry and cytotoxic activity of CTLs provide feasible
therapeutic approaches to reduce viral infections, which may eventually lead to
the elimination of chronic infections such as HIV, HBV and EBV.