Abstract
BackgroundReduced thymic function causes poor immunological reconstitution in human immunodeficiency virus (HIV)-positive patients on combined antiretroviral therapy (cART). The association between immune activation and thymic function in asymptomatic HIV-positive treatment-naive individuals has thus far not been investigated.Aims and objectivesTo optimise a five-colour flow cytometric assay for measurement of thymic function by measuring recent thymic emigrants (RTEs) in treatment-naive HIV-infected patients and healthy controls and correlate results with levels of immune activation, CD4 counts and viral load.MethodsBlood obtained from 53 consenting HIV-positive individuals and 32 controls recruited from HIV prevention and testing clinic in Cape Town, South Africa. RTEs were measured (CD3+/CD4+/CD45RA+/CD31+/CD62L+) and levels were correlated with CD4 counts of HIV-infected individuals, log viral load and levels of immune activation (CD8+/CD38+ T-cells).ResultsHIV-infected individuals had reduced frequencies of RTEs when compared to controls (p = 0.0035). Levels of immune activation were inversely correlated with thymic function (p = 0.0403), and the thymic function in HIV-infected individuals showed no significant correlation with CD4 counts (p = 0.31559) and viral load (p = 0.20628).ConclusionsThere was impaired thymic function in HIV-infected individuals, which was associated with increased levels of immune activation. The thymic dysfunction was not associated with CD4 counts and viral load. Immune activation may result in inflammatory damage to the thymus and subsequent thymic dysfunction, and CD4 counts and viral load may not necessarily reflect thymic dysfunction in HIV.
Highlights
BackgroundHuman immunodeficiency virus (HIV) infection is characterised by depletion of naive and memory CD4 T-cells due to its ability to damage both thymic and peripheral T-cell homeostasis
recent thymic emigrants (RTEs) were significantly reduced in the human immunodeficiency virus (HIV)-infected group, with mean % value of 40.13 ± 21.72 in HIV-positive group versus 54.96 ± 20.10 in control group (p = 0.0035). (The bars depict standard deviations and the lines are mean %.)
There were no significant correlations between age in the HIVpositive cohort and other parameters such as CD4 counts, viral load, levels of immune activation and RTEs in this group, and RTEs did not show a significant correlation with the CD4 counts or the log viral load
Summary
Human immunodeficiency virus (HIV) infection is characterised by depletion of naive and memory CD4 T-cells due to its ability to damage both thymic and peripheral T-cell homeostasis. There is evidence of direct infection of thymocytes by HIV, which results in defective thymopoiesis and apoptosis of CD4 T-cells.[1,2]. Within a year of initiation of combined antiretroviral therapy (cART), the thymus of adult HIVpositive patients on cART expands,[3] and evidence has shown that infected adults’ thymuses are still functional despite physiological involution. The thymus plays a role in immune recovery or contributes to the lack of immune reconstitution in HIV-infected patients.[4] In some studies, it has been shown that immune reconstitution in adults is mainly from the memory T-cell pool, whereas in children, it is mainly from the naive T-cell subset.[5]
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