A Population of CD4+CD8+ Double-Positive T Cells Associated with Risk of Plasma Leakage in Dengue Viral Infection

Abstract

According to the WHO 2009 classification, dengue with warning signs is at the risk of developing severe form of dengue disease. One of the most important warning signs is plasma leakage, which can be a serious complication associated with higher morbidity and mortality. We report that the frequency of CD4+CD8+ double-positive (DP) T cells is significantly increased in patients at risk of developing plasma leakage. Transcriptomic analysis demonstrated that CD4+CD8+ DP cells were distinct from CD4+ Single Positive (SP) T cells but co-clustered with CD8+ SP cells, indicating a largely similar transcriptional profile. Twenty significant differentially expressed (DE) genes were identified between CD4+CD8+ DP and CD8+ SP cells. These genes encode OX40 and CCR4 proteins as well as other molecules associated with cell signaling on the cell surface (NT5E, MXRA8, and PTPRK). While comparing the profile of gene expression in CD4+CD8+ DP cells from patients with and without warning signs of plasma leakage, similar expression profile was observed, implying a role of CD4+CD8+ DP cells in plasma leakage through a quantitative increase rather than functional alteration. This study provided novel insight into the host immune response during the acute febrile phase of DENV infection and the role of CD4+CD8+ DP T cells in the pathogenesis of plasma leakage.

Innate adaptive immune cell dynamics in tonsillar tissues during chronic SIV infection

“…However, evidence indicates that in vivo terminally differentiated effector CD4 + may acquire the α-chain of CD8. DP T cells have been higher in HIV ( 34 , 35 ) and other viral infections ( 36 , 37 ) autoimmune and chronic inflammatory disorders ( 38 , 39 ). Here we report significantly higher DP T in chronic SIV infected macaques’ tonsils.…”

Determining reference ranges for immunological cells of healthy indigenous individuals from a region in Brazil

“…The lymphocyte reference range results of healthy individuals in different countries worldwide present different results associated with ethnic groups, showing the importance of obtaining specific evaluation parameters for different racial patterns. ( 23 , 25 - 29 )…”

Increased CD4+CD8+ Double Positive T Cells during Hantaan Virus Infection

“…Although we proved the antiviral potentials of DP T cells in our study, the roles of DP T cells during HTNV infection were still need further study. Yu et al identified the DP T cells in Dengue virus infection as a potential marker of plasma leakage progression to shock and may contribute to the pathogenesis of disease [ 23 ]. We also studied the correlation between dynamic changes of DP T cells and clinical indicators of HFRS patients.…”

“…During Dengue virus infection, frequency of DP T cells was significantly increased. Instead of against virus, they were believed to contributed to the pathogenesis of plasma leakage [ 23 ]. In rheumatoid arthritis (RA), DP T cells were recognized as inflammatory cells and contributed to disease pathogenesis [ 24 ].…”