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Follicular CXCR5-expressing CD8+ T cells curtail chronic viral infection
 
 
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Nature August 3 2016
 
"given the largely shared mechanisms of T cell exhaustion between chronic viral infection and cancer 28-30, this study may shed new light on cancer immunotherapy."
 
Abstract
 
During chronic viral infection, virus-specific CD8+ T cells become exhausted, exhibit poor effector function and lose memory potential1-4. Nevertheless, exhausted CD8+ T cells can still contain viral replication in chronic infections5-9, although the mechanism is largely unknown. Here we show that a subset of exhausted CD8+ T cells expressing the chemokine receptor CXCR5 plays a critical role in the control of viral replication in mice that were chronically infected with lymphocytic choriomeningitis virus (LCMV). These CXCR5+CD8+ T cells were preferentially localized in B-cell follicles, expressed lower levels of inhibitory receptors and exhibited more potent cytotoxicity than the CXCR5- subset. Furthermore, we identified the Id2/E2A axis as an important regulator for the generation of this subset. In HIV patients, we also identified a virus-specific CXCR5+CD8+ T cell subset, and its number was inversely correlated with viral load. The CXCR5+ subset showed greater therapeutic potential than the CXCR5- subset when adoptively transferred to chronically infected mice and exhibited the synergistic effect on reducing viral load when combined with anti-PD-L1 treatment. This study defines a unique subset of exhausted CD8+ T cells that plays a pivotal role in the control of viral replication during chronic viral infection.
 
 
 
 
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