Reduced CD4 T cell activation and in vitro susceptibility to HIV-1 infection in exposed uninfected Central Africans

Abstract

Background: Environmentally driven immune activation was suggested to contribute to high rates of HIV-1 infection in Africa. We report here a study of immune activation markers and susceptibility to HIV-1 infection in vitro of forty-five highly exposed uninfected partners (EUs) of HIV-1 infected individuals in Central African Republic, in comparison with forty-four low-risk blood donors (UCs).

Results: Analysis of T lymphocyte subsets and activation markers in whole blood showed that the absolute values and the percentage of HLA-DR+CD4 T cells and of CCR5+CD4 T cells were lower in the EUs than in the UCs (p = 0.0001). Mutations in the CCR5 coding region were not found in either group. Susceptibility to in vitro infection of unstimulated peripheral blood mononuclear cells, prior of PHA activation, was decreased in EUs compared to UCs, either using a CXCR4-tropic or a CCR5-tropic HIV-1 strain (p = 0.02 and p = 0.05, respectively). Levels of MIP-1beta, but not of MIP-1alpha or RANTES, in the supernatants of PHA-activated PBMC, were higher in the EUs than in the UCs (p = 0.007).

Conclusion: We found low levels of CD4 T cell activation and reduced PBMC susceptibility to HIV-1 infection in Central African EUs, indicating that both may contribute to the resistance to HIV-1 infection.

Figure 1

Susceptibility of peripheral blood mononuclear cells to in vitro HIV-1 infection. PBMCs (10⁵ cells/well in 96-well microplates) from 45 EUs and 44 UCs were infected with HIV-1 NL-4.3 (A) or with HIV-1 BaL (B) in quadruplicate. Infections were performed either 24 h before PHA activation of PBMC (BA), or after 3-days PHA activation (AA). Standard PBMC were infected in parallel in each assay. HIV-1 replication was monitored by p24 antigen measure in culture supernatants. The p24 values of each individual PBMC infection were compared to the mean p24 value of standard PBMC. Results are expressed as the percent of the standard PBMC supernatant p24 at the peak of infection. Box-plots represent the 25^th and the 75^th percentiles and bars indicate the lowest and the highest values. The horizontal line in the boxes indicates the median. Comparisons between the groups were made using the non parametric Mann-Whitney U test.

Figure 2

β-chemokine levels in PBMC supernatants. PBMC culture supernatants were collected after a 3-day-PHA-activation and levels of MIP-1α/CCL3, MIP-1β/CCL4 and RANTES/CCL5 were measured by ELISA. Box-plots show the median values and percentiles of the levels of each β-chemokine expressed in ng/ml. Comparisons between the groups were made using the Mann-Whitney U test.