Background Chronic HIV-1 infection is characterised by immune activation and exhaustion. This study investigated B-cell subset distribution and novel markers of immune activation and exhaustion in an asymptomatic untreated HIV-infected cohort; and VIP’s effect thereon. The immunomodulator, VIP, is known to limit T-cell activation. No studies to date have examined VIP’s on B-cell activation in the context of HIV infection.
Methods HIV+ patients and matched HIV- controls were recruited at Emavudleni, a voluntary HIV testing and prevention clinic in Crossroads, Cape Town. B-cells were isolated via RosetteSep enrichment; cultured for 18h with either LPS, or R848 alone, or with VIP; and then analysed via BD FACSCanto II. B-cell subsets were as follows: activated memory (AM), resting memory (RM: CD21+CD27+), mature naïve (MN: CD21+CD27-), or tissue-like memory (TLM: CD21loCD27lo). Surface expression of markers of activation (CD126, CD86, CD38, CD284) exhaustion (CD72, CD85j, CD305, CD300a, CD307d), and apoptosis signalling (CD95) were measured. These were also compared to standard markers of immune activation (CD38+CD8+ T-cells) and HIV infection (CD4 count and plasma viral load).
Results RM was decreased, while TLM was increased (p < 0.01) with HIV-infection. CD126 & CD86 expression on AM & RM decreased by 20% with VIP inhibition; while AM, RM, TLM & MN CD72 expression decreased by 63%. CD85j AM & TLM expression decreased by 45%, & CD95 expression on RM, TLM, & MN decreased by 52% with VIP inhibition (all p < 0.001).
Conclusion Our data indicated that B-cells are in a more activated state and possibly more prone to apoptosis in untreated, asymptomatic HIV, and that addition of VIP resulted in a near complete down-regulation of markers associated with activation, exhaustion, and apoptosis. VIP is a potentially valuable novel immunnomodulatory agent for the limitation of B-cell activation, alleviation of exhaustion and selective modulation of apoptosis in asymptomatic HIV infection.
- Immune activation
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