HIV-1 vaccine functioning relies on successful induction of broadly neutralizing antibodies (bNAbs). CXCR3− circulatory T-follicular helper (cTfh) cells are necessary for inducing B-cells for generating bNAbs. Recent studies have suggested that CXCR3+ Tfh cells might also influence bNAb production. Plasma samples from 34 ART-Naïve HIV-1 infected individuals [long-term nonprogressors (LTNP)—19; Progressors—13] were tested against a heterologous virus panel (n = 11) from subtypes A, B, C, G, AC, BC and AE. Frequencies of CXCR3+ and CXCR3− cTfh-like cells in peripheral circulation were studied using flow cytometry. LTNP showed significantly lower CXCR3+ and higher CXCR3− cTfh-like cell frequencies, while neutralization breadth was observed to be broader in progressors. A positive correlation was observed between bNAb breadth and potency with CXCR3+PD-1+ cTfh-like cells in LTNP. Based on neutralization breadth, 9 HIV-1 infected individuals were classified as ‘top neutralizers’ and 23 as ‘low neutralizers’ and they did not show any correlations with CXCR3+ and CXCR3− cTfh-like cells. These preliminary data suggest that CXCR3+ similar to CXCR3− might possess significant functional properties for driving B-cells to produce bNAbs. Hence, an HIV vaccine which is capable of optimal induction of CXCR3+ cTfh cells at germinal centers might confer superior protection against HIV.
Background:
Anti-viral cytokine expressions by cytotoxic T-cells and lower activation
rates have been reported to correlate with suppressed HIV replication in long-term non-progressors
(LTNP). Immune mechanisms underlying disease non-progression in LTNP might vary with HIV-1
subtype and geographical locations.
Objective:
This study evaluates cytokine expression and T-cells activation in relation to disease
non-progression in LTNP.
Methods:
HIV-1 Subtype C infected LTNP (n=20) and progressors (n=15) were enrolled and
flowcytometry assays were performed to study HIV-specific CD8 T-cells expressing IL-2, IFN-γ,
TNF-α and MIP-1β against gag and env peptides. CD4+ T-cell activation was evaluated by surface
expression of HLADR and CD38.
Results:
Proportions of cytokines studied did not differ significantly between LTNP and
progressors, while contrasting correlations with disease progression markers were observed in
LTNP. CD4+ T-cell activation rates were significantly lower in LTNP compared to progressors
which indicate the potential role of T-cell activation rates in disease non-progression in LTNP.
Conclusion:
LTNP and progressors showed similar CD8+ T-cell responses, but final conclusions
can be drawn only by comparing multiple immune factors in larger LTNP cohort with HIV-1 infected
individuals at various levels of disease progression. A possible role of HIV-1 subtype variation
and ethnic differences in addition to host-genetic and viral factors cannot be ruled out.
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