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Wim Jennes

Publications and source records attributed to Wim Jennes.

10 recordsLinked to original sources
PubMed2006

Cutting edge: resistance to HIV-1 infection among African female sex workers is associated with inhibitory KIR in the absence of their HLA ligands.

NK cells are regulated in part by killer Ig-like receptors (KIR) that interact with HLA molecules on potential target cells. KIR and HLA loci are highly polymorphic and certain KIR/HLA combinations were found to protect against HIV disease progression. We show in this study that KIR/HLA interactions also influence resistance to HIV transmission. HIV-exposed but seronegative female sex workers in Abidjan, Côte d'Ivoire, frequently possessed inhibitory KIR genes in the absence of their cognate HLA genes: KIR2DL2/KIR2DL3 heterozygosity in the absence of HLA-C1 and KIR3DL1 homozygosity in the absence of HLA-Bw4. HIV-seropositive female sex workers were characterized by corresponding inhibitory KIR/HLA pairings: KIR2DL3 homozygosity together with HLA-C1 and a trend toward KIR3DL1/HLA-Bw4 homozygosity. Absence of ligands for inhibitory KIR could lower the threshold for NK cell activation. In addition, exposed seronegatives more frequently possessed AB KIR genotypes, which contain more activating KIR. The data support an important role for NK cells and KIR/HLA interactions in antiviral immunity.

Adult↗
PubMed2006

The predominance of Human Immunodeficiency Virus type 1 (HIV-1) circulating recombinant form 02 (CRF02_AG) in West Central Africa may be related to its replicative fitness.

BACKGROUND: CRF02_AG is the predominant HIV strain circulating in West and West Central Africa. The aim of this study was to test whether this predominance is associated with a higher in vitro replicative fitness relative to parental subtype A and G viruses. Primary HIV-1 isolates (10 CRF02_AG, 5 subtype A and 5 subtype G) were obtained from a well-described Cameroonian cohort. Growth competition experiments were carried out at equal multiplicity of infection in activated T cells and monocyte-derived dendritic cells (MO-DC) in parallel. RESULTS: Dual infection/competition experiments in activated T cells clearly indicated that CRF02_AG isolates had a significant replication advantage over the subtype A and subtype G viruses. The higher fitness of CRF02_AG was evident for isolates from patients with CD4+ T cell counts >200 cells/microL (non-AIDS) or CD4+ T cell counts <200 cells/microL (AIDS), and was independent of the co-receptor tropism. In MO-DC cultures, CRF02_AG isolates showed a slightly but not significantly higher replication advantage compared to subtype A or G isolates. CONCLUSION: We observed a higher ex vivo replicative fitness of CRF02_AG isolates compared to subtype A and G viruses from the same geographic region and showed that this was independent of the co-receptor tropism and irrespective of high or low CD4+ T cell count. This advantage in replicative fitness may contribute to the dominant spread of CRF02_AG over A and G subtypes in West and West Central Africa.

CD4-Positive T-Lymphocytes↗
PubMed2006

Dominant ex vivo cross-stimulation of CD8+ T-cells with whole soluble gag protein in HIV-infected subjects.

BACKGROUND: Soluble HIV proteins are often used to detect HIV-specific CD4+ T-helper cell responses in vitro. However, exogenous antigens can also indirectly stimulate CD8+ T-cells and thus complicate assessment of CD4+ T-cell responses. OBJECTIVE: To analyze the extent of in vitro HIV-1 Gag p55 protein cross-stimulation to CD8+ T-cells in therapy-naive and highly active antiretroviral therapy (HAART)-treated HIV patients and to correlate this phenomenon with HIV disease progression. METHODS: Gag protein-stimulated T-cell responses were measured in total and CD8-depleted peripheral blood mononuclear cells (PBMCs) by interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) assays in 20 therapy-naive and 60 HAART-treated HIV patients. Numbers of spot forming cells (SFCs) relative to CD4+ and CD8+ T-cell subsets were calculated. Gag protein-stimulated responses were correlated with markers of disease progression. RESULTS: Stimulation of PBMC with HIV-1 Gag protein induced higher CD8+ T-cell responses than CD4+ T-cell responses in both therapy-naive and HAART-treated HIV patients (P < 0.001). Gag protein cross-stimulation of CD8+ T-cells was higher in therapy-naive than in HAART-treated HIV patients (P < 0.001). In HAART-treated HIV patients, we detected an inverse correlation between Gag protein cross-stimulation of CD8+ T-cells and the CD4 count (R = -0.311; P = 0.016). Depletion of CD14+ cells abrogated the responses, suggesting that Gag protein cross-stimulation of CD8+ T-cells depends on antigen processing and presentation by antigen-presenting cells (APCs). CONCLUSIONS: HIV protein cross-presentation to CD8+ T-cells should be taken into account when detecting HIV-specific T-cell responses by stimulation of PBMCs with whole exogenous antigens.

Antiretroviral Therapy, Highly Active↗
PubMed2004

Poorly soluble peptides can mimic authentic ELISPOT responses.

The ELISPOT assay is a specific, sensitive, quantitative assay for assessing cell-mediated immune responses to a variety of antigens including HIV-1 peptides. In an interferon (IFN)-gamma-ELISPOT assay, peripheral blood mononuclear cells (PBMC) from two HIV-1 exposed seronegative (ESN) individuals appeared to respond strongly to an HIV Gag peptide. Analysis of this peptide revealed that it was incompletely dissolved and induced non-specific spot formation, even in the absence of cells. In subsequent experiments, the peptide was found to interact with avidin and the ELISPOT membrane. Filtering the peptide prevented non-specific spot formation. These findings underscore the need for appropriate controls and proper peptide preparation in order to reduce the risk of false-positive ELISPOT responses.

Amino Acid Sequence↗
PubMed2004

HIV-specific T helper responses and frequency of exposure among HIV-exposed seronegative female sex workers in Abidjan, Cote d'Ivoire.

BACKGROUND: The characteristics of human immunodeficiency virus (HIV) exposure that determine the induction of HIV-specific T cells and, in particular, T helper cells are not well understood. METHODS: HIV-1 Gag- and Env-specific T helper cells were analyzed by use of an interferon (IFN)- gamma enzyme-linked immunosorbent spot (ELISPOT) assay and by use of IFN- gamma secretion flow cytometry. Responses among HIV-exposed seronegative (ESN) female sex workers (FSWs) were compared with responses among HIV-seropositive FSWs and HIV-seronegative female blood donors from Abidjan, Cote d'Ivoire. RESULTS: Low-level ELISPOT responses were detected in 8 (20%) of 40 ESN FSWs. All of 25 HIV-seropositive FSWs had high-level ELISPOT responses. HIV-specific CD4+ T cells and, occasionally, CD8+ T cells were detected by secretion flow cytometry in 3 (38%) of 8 ESN FSWs and in 4 (80%) of 5 HIV-seropositive FSWs. ESN FSWs with detectable HIV-specific T helper responses had more clients on the previous working day (P=.02) and more exposures to HIV per month (P=.02) and tended to have a lower total duration of commercial sex work. CONCLUSIONS: These findings demonstrate that the presence of HIV-specific T helper cells in ESN FSWs is associated with the frequency, rather than the duration, of exposure to HIV. The data may have important implications for the evaluation of HIV vaccine efficacy.

Adult↗
PubMed2004

Disturbed secretory capacity for macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta in progressive HIV infection.

The protective role of beta-chemokines in HIV infection and disease remains controversial. Contradictory findings have been reported possibly as the result of different beta-chemokine detection methods. To test this, peripheral blood lymphocytes from treatment-naive HIV patients, patients on highly active antiretroviral therapy (HAART), and uninfected controls were assessed for intracellular beta-chemokine levels in comparison with levels of beta-chemokine secretion in culture supernatants. HIV patients had significantly higher intracellular levels of macrophages inflammatory protein (MIP)-1 alpha and MIP-1 beta than uninfected control subjects. In contrast, MIP-1 alpha and MIP-1 beta supernatant levels were significantly lower in HIV patients than in controls. Interestingly, both intracellular and supernatant levels of RANTES (regulated on activation, normal T cell expressed and secreted) were significantly increased in HIV patients. Prolonged (> 3 years) administration of HAART in HIV patients normalized the intracellular levels of MIP-1 beta and RANTES and restored the decreased supernatant levels of MIP-1 alpha and MIP-1 beta to levels observed among controls. Significant direct correlations observed between the intracellular and the supernatant levels of beta-chemokines in controls were lost in treatment-naive (except MIP-1 beta) and HAART-treated patients (except RANTES after 3 years of HAART). These data indicate that lymphocytes of HIV patients display a disrupted capacity to secrete the beta-chemokines MIP-1 alpha and MIP-1 beta, which may constitute a mechanism of immune dysfunction in progressive HIV infection. Furthermore, we demonstrated that the detection of beta-chemokines in HIV patients by different methods may indeed result in contradictory findings.

Antiretroviral Therapy, Highly Active↗
PubMed2002

Cellular human immunodeficiency virus (HIV)-protective factors: a comparison of HIV-exposed seronegative female sex workers and female blood donors in Abidjan, Côte d'Ivoire.

Cellular factors that may protect against human immunodeficiency virus (HIV) infection were investigated in 27 HIV-exposed seronegative (ESN) female sex workers (FSWs) and 27 HIV-seronegative female blood donors. Compared with blood donors, ESN FSWs had significantly decreased expression levels of C-X-C chemokine receptor 4 (CXCR4), but not of C-C chemokine receptor 5, on both memory (P<.001) and naive (P=.041) CD4(+) T cells. CXCR4 down-regulation was associated with prolonged duration of commercial sex work by ESN FSWs. CD38 expression on CD8(+) T cells was significantly increased among ESN FSWs, compared with that among blood donors (P=.017). There were no differences in HLA-DR and CD62L expression between blood donors and ESN FSWs. Proportions of T cells producing the beta-chemokines RANTES (regulated on activation, normally T cell-expressed and -secreted), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta or the cytokines interleukin (IL)-2, IL-4, interferon-gamma, and tumor necrosis factor-alpha, were similar in the 2 groups. These data indicate that ESN FSWs differ from HIV-seronegative female blood donors with respect to immunological factors that have no clear protective potential against HIV transmission.

Adolescent↗
PubMed2002

Enhanced ELISPOT detection of antigen-specific T cell responses from cryopreserved specimens with addition of both IL-7 and IL-15--the Amplispot assay.

The importance of the enzyme-linked immunosorbent spot (ELISPOT) assay as a tool for studying immune responses in vitro is becoming increasingly apparent. However, there remains a need for enhanced sensitivity for the detection of low frequency antigen-specific T cell responses. We reasoned that the addition of a combination of the cytokines interleukin (IL)-7 and IL-15 would selectively increase interferon-gamma (IFN-gamma) production from antigen-stimulated CD4+ and CD8+ effector memory T cells. Freshly isolated or cryopreserved peripheral blood mononuclear cells (PBMC) from four healthy donors were analysed by ELISPOT for the frequency of purified protein derivative (PPD)-specific CD4+ T cells or cytomegalovirus (CMV) peptide-specific CD8+ T cells. Addition of IL-7 and IL-15 increased the number of PPD-specific CD4+ T cells up to 2.4-fold in fresh PBMC and up to 18-fold in cryopreserved PBMC. The cytokines also increased the number of CMV peptide-specific CD8+ T cells in fresh PBMC up to 7.5-fold. No additional increases were seen when antibodies to co-stimulatory molecules CD28 and CD49d were applied together with the cytokine combination. These data demonstrate that the sensitivity of the ELISPOT assay may be significantly augmented by addition of the cytokines IL-7 and IL-15 to antigen-stimulated cells. This method will be particularly useful for the assessment of antigen-stimulated cytokine production by T cells in cryopreserved biological specimens.

Antigens↗
PubMed2002

Positive association between beta-chemokine-producing T cells and HIV type 1 viral load in HIV-infected subjects in Abidjan, Côte d'Ivoire.

The role of beta-chemokines in controlling HIV replication in vivo is still controversial. Therefore, the association between HIV-1 plasma viral load and the capacity of CD4(+) and CD8(+) T cells to produce beta-chemokines was studied in 28 antiretroviral drug-naïve HIV-1-infected female sex workers in Abidjan, Côte d'Ivoire. Percentages of beta-chemokine-positive T cells were measured in peripheral blood mononuclear cells by flow cytometry after intracellular staining for RANTES (regulated on activation, normal T expressed and secreted), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta. HIV-1-infected subjects had higher percentages of MIP-1alpha- and MIP-1beta-positive CD4(+) and CD8(+) T cells (p < 0.02) and of RANTES-positive CD8(+) T cells (p = 0.054) than uninfected controls. Percentages of RANTES- and MIP-1beta-positive CD8(+) T cells correlated directly with HIV-1 plasma viral load (p < 0.02). Percentages of beta-chemokine-positive CD4(+) and CD8(+) T cells correlated directly with percentages of HLA-DR-positive T cells (p < 0.02) and inversely (except RANTES in CD4(+) T cells) with absolute numbers of CD4(+) T cells (p < 0.05) in peripheral blood. These data indicate that increased percentages of beta-chemokine-producing T cells in HIV-1-infected subjects correlate with disease progression and are a sign of viremia-driven chronic T cell activation.

Adult↗