Schistosoma haematobium infection and Buruli ulcer.
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Animals↗
Biomedical subjects
Luc Kestens
Publications and source records attributed to Luc Kestens.
Human and simian immunodeficiency virus-infected chimpanzees do not have increased intracellular levels of beta-chemokines in contrast to infected humans.
This study was undertaken to explain why chimpanzees infected with HIV-1 (human immunodeficiency virus type 1) or SIV(cpz) (simian immunodeficiency virus of chimpanzee) are relatively resistant to AIDS (acquired immunodeficiency syndrome). The numbers of beta-chemokine-positive cells were compared between uninfected and infected humans and chimpanzees using three-color cytofluorometry. In humans, the percentage of beta-chemokine-positive cells was significantly higher in CD8(+) T and natural killer (NK) cells than in CD4(+) T cells in both uninfected and HIV-1-infected individuals. In the presence of HIV-1 infection, however, both CD8(+) and CD4(+) T cell subsets contained significantly more beta-chemokine-positive cells than in the absence of infection. Interestingly, in chimpanzees two important differences were noted. First, their percentage of beta-chemokine-positive CD8(+) T and NK cells was significantly higher than in uninfected humans. Second, in contrast to humans, infection with either HIV-1 or with SIV(cpz) was not associated with increased numbers of beta-chemokine-positive cells. These results indicate that: constitutive high levels of intracellular beta-chemokines in chimpanzees' CD8 lymphocytes and NK cells do not necessarily correspond to lower levels of virus replication during the chronic phase of infection; and increased percentages of beta-chemokine-positive cells in HIV-infection are not a correlate of disease resistance. The data suggest that neither pre-nor post-exposure levels of intracellular beta-chemokines are correlated with the subsequent control of disease progression.
Animals↗
Changes in levels of immune activation and reconstitution markers among HIV-1-infected Africans receiving antiretroviral therapy.
OBJECTIVE: To describe changes in immune activation and reconstitution markers among HIV-1-infected patients receiving antiretroviral therapy (ART) in Abidjan, Côte d'Ivoire. METHODS: Between November 1998 and February 2001, we analyzed changes in immune activation and reconstitution markers among 52 patients. Good virologic responders (n = 26) were defined as those who had suppressed and maintained plasma viral load (VL) below the detection limit of the assay for at least 12 months. Poor virologic responders (n = 26) were defined as those with a detectable VL at 6 and 12 months after beginning ART. RESULTS: Of the 26 good virologic responders, 20 (77%) were on highly active antiretroviral therapy (HAART) compared with one (4%) of the poor responders. Among the 26 good responders, baseline median levels of CD38+CD8+ T cells were elevated, but had decreased significantly at 6 months (P < 0.001) and at 12 months of therapy (P < 0.001). Median levels of HLA-DR+CD8+ T cells also decreased from baseline at 6 months (P < 0.001) and at 12 months of therapy (P < 0.001). Levels of CD62L+CD4+ T cells increased steadily during the 6 and 12 months of therapy and reached levels observed among HIV-negative blood donors (P = 0.07). Among the 26 poor responders, median levels of CD38+CD8+ T cells decreased significantly at 12 months of therapy (P = 0.006), but were higher than levels in blood donors (P = 0.005). Levels of HLA-DR+CD8+ T cells decreased significantly at 12 months of therapy (P < 0.001). Levels of CD62L+CD4+ decreased over time. CONCLUSION: Our results suggest that HAART can be successfully used in African populations with elevated baseline immune activation markers.
ADP-ribosyl Cyclase↗
National external quality assessment scheme for lymphocyte immunophenotyping in Belgium.
In 2000, the Belgian Scientific Institute of Public Health introduced a voluntary external quality assessment scheme for lymphocyte immunophenotyping. This paper provides an analysis of the first six surveys. Specimens consisted of fresh EDTA-anticoagulated whole blood and were sent by overnight mail. The 41 participants were surveyed for methodology and were asked to report white blood cell count, percentage of lymphocytes, and percentages and absolute numbers of CD3+, CD4+, CD8+, and CD19+ cells. Median intralaboratory coefficients of variation were 1.0, 1.3, 1.7, and 3.2% for CD3+, CD4+, CD8+, and CD19+ cell percentages, respectively. Interlaboratory variability was consistently lower than 6.5% for CD3+ and CD4+CD3+ cell percentages, and lower than 9.5% for CD8+CD3+ cell percentages. Median coefficients of variation for the absolute values were higher, ranging from 10.1% for CD4+CD3+ cells to 16.5% for CD19+ cells. The percentage of CD4+CD3+ and CD8+ CD3+ cells was in several samples significantly lower than the percentage of total CD4+ and CD8+ cells. The number of laboratories measuring total CD4+ and CD8+ cells decreased by 30% during the programme. Between-laboratory variability remained stable over time. Analysis of individual laboratory performance indicated that some laboratories markedly improved their results.
Antigens, CD↗
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↗
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↗
Activity of reverse transcriptase inhibitors in monocyte-derived dendritic cells: a possible in vitro model for postexposure prophylaxis of sexual HIV transmission.
Because prevention of heterosexual HIV transmission is not always possible, it is important to develop effective strategies of postexposure prophylaxis (PEP). Since in vivo comparison of drug potency is difficult, we developed an in vitro model with cells resembling primary targets during sexual transmission: monocyte-derived dendritic cells (MO-DCs), Langerhans cells (MO-LCs), and resting autologous CD4(+) T cells. Nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs, respectively) were evaluated for their antiviral activity, when added immediately after infection or at a later time point. In parallel, their immune-suppressive effect was examined by measuring inhibition of mixed MO-DC/allogeneic CD4(+) T cell cultures. Most RTIs potently inhibited HIV replication, even if added 24 hr after infection (representing PEP). The sensitivity to antiretroviral drugs was similar in HIV-infected MO-DCs and MO-LCs, but decreased in cocultures with resting autologous CD4(+) T cells. The NNRTIs efavirenz and UC-781 as well as the NRTIs AZT, 3TC, and d4T showed a similar high potency in MO-DC plus autologous CD4(+) T cell cocultures as compared with CEM T cells, whereas their activity in phytohemagglutinin/interleukin 2 (PHA/IL-2)-activated CD4(+) T cells was lower. The dideoxynucleoside RTI abacavir as well as the phosphonates (R)-PMPA and PMEA were more active in infected MO-DCs as compared with either CEM T cells or PHA/IL-2 activated CD4(+) T cells. Infection in cocultures of MO-DCs and autologous CD4(+) T cells could be aborted in a proportion of the cultures, with high concentrations of PMEA and/or efavirenz, but not with AZT. Suppressive activity in mixed leukocyte cultures was observed only at very high concentrations of RTI. Our data suggest that cocultures of MO-DCs and autologous CD4(+) T cells can be used as a possible in vitro model to explore protocols for PEP after sexual HIV transmission.
Anti-HIV Agents↗
Disseminated Mycobacterium ulcerans disease in an HIV-positive patient: a case study.
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AIDS-Related Opportunistic Infections↗
In vitro replication of SIVcpz is suppressed by beta-chemokines and CD8+ T cells but not by natural killer cells of infected chimpanzees.
Unlike humans, chimpanzees are relatively resistant to AIDS after infection with HIV-1 or simian immunodeficiency virus of chimpanzee (SIVcpz). We hypothesized that resistance to disease progression is associated with efficient suppression of virus replication possibly by beta-chemokines secreted by CD8+ lymphocytes and especially natural killer (NK) cells. In vitro suppression of virus replication can be easily studied in SIVcpz-infected chimpanzees because they produce high infectious virus titers in their peripheral blood. A study was undertaken to assess the sensitivity of SIVcpz to beta-chemokines in vitro and to investigate the role of endogenous beta-chemokines in relation to the in vitro capacity of CD8+ lymphocytes and NK cells of chimpanzees to suppress SIVcpz replication. Our results show that SIVcpz uses CCR5 as a coreceptor to gain cell entry and is sensitive to recombinant beta-chemokines in vitro. Here we report that despite their potent capacity to produce RANTES, NK cells of infected chimpanzees do not suppress SIVcpz replication in vitro, in contrast to CD8+ lymphocytes. We also show that endogenous beta-chemokines are not the predominant factors mediating in vitro suppression.
Animals↗
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↗
In vitro susceptibility to infection with SIVcpz and HIV-1 is lower in chimpanzee than in human peripheral blood mononuclear cells.
This study was undertaken to evaluate and compare the susceptibility of chimpanzee versus human peripheral blood mononuclear cells (PBMCs) to infection with SIVcpz and HIV-1 non-syncitium inducing primary isolates. The results demonstrate clearly that chimpanzee PBMCs have a lower capacity to support viral replication as compared to human PBMCs. There was no experimental evidence that this difference was due to a lower availability of target cells for viral infection (PBMCs positive for CD4 and CCR5 molecules) or to a differential susceptibility to apoptosis (PBMCs positive for CD4 and CD95 molecules). A lower capacity of chimpanzee PBMCs to support SIVcpz and HIV-1 replication in vitro is related to a post-entry barrier to virus replication.
Animals↗