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Biomedical subjects

L Kestens

Publications and source records attributed to L Kestens.

At least 73 records · Page 4Linked to original sources

Subset markers of CD8(+) cells and their relation to enhanced cytotoxic T-cell activity during human immunodeficiency virus infection.

Using fresh whole blood or isolated lymphocytes, the activity of in vivo generated cytotoxic T-lymphocytes (CTL) was measured as the OKT3-specific lysis of HL-60 targets, in a cross-sectional study of 53 HIV (+) patients. CTL activity in the entire HIV(+) group was two to three times higher than in HIV(-) controls, with WHO stage 3 (=pre-AIDS) patients showing the highest cytolytic function. The whole-blood CTL assay was validated and its practical and theoretical advantages are discussed. Within the CD8(+) cells, the number and proportion of the CD45RO(+) "memory" subset were significantly increased in HIV(+) subjects. The HLA-DR(+) subset rose most spectacularly in the asymptomatic stage of the infection, while the CD38(+) subset was the only one still significantly rising between the pre-AIDS and the AIDS stage. CTL activity was most closely correlated with T8 cells expressing the CD38 marker. In the context of CTL, CD38 thus seems to reflect activation rather than immaturity. Lymphocytes from HIV(+) subjects with a high OKT3-specific lytic capacity also destroyed normal lymphoblasts to a significant extent, pointing to their possible involvement in an autodestructive process. Our data thus suggest the importance of T8 cytolytic function and/or T8 subtyping in the immunopathogenesis and the prognosis of HIV infection.

ADP-ribosyl Cyclase↗

HIV antigen detection in circulating immune complexes.

Various methods were evaluated for their effectiveness in releasing HIV antigen (Ag) from artificial immune complexes (IC) and from IC present in serum from HIV antibody (Ab) positive subjects. The most effective methods for recovering HIV Ag from IC were those which included a denaturation step to prevent reassociation of Ag with Ab. IC precipitation in 2.5% polyethylene glycol followed by acid treatment with 1 M glycine.HCl (pH 2) for 10 min at 70 degrees C in the presence of 0.05% SDS gave very satisfactory results. With this method, IC were detected in sera from HIV antibody positive Caucasian subjects at all stages of infection. After HIV IC dissociation, HIV Ag was detected in a significant number (8/17 or 47%) of asymptomatic subjects. IC were most prevalent during the late stages of infection. A substantial increase in HIV Ag positivity was also observed in 20 Senegalese HIV Ab positive sera. After HIV IC dissociation HIV antigen detection increased from 2/20 to 12/20. The relevance of IC detection is discussed.

Antigen-Antibody Complex↗

Evidence for circulating activated cytotoxic T cells in HIV-infected subjects before the onset of opportunistic infections.

The activity of both cytotoxic T lymphocyte (CTL) and natural killer (NK) cells were measured cross-sectionally in 43 subjects seropositive for HIV, in 27 HIV- blood donors and in 24 HIV- persons from the Outpatients Clinic for sexually transmitted diseases. CTL activity was evaluated using the HL-60 cells coated with OKT3 as the targets and freshly separated peripheral blood lymphocytes as the effectors. In 20 out of 43 HIV+ subjects, CTL activity was significantly enhanced in comparison to the HIV- subjects. This lytic activity correlated positively with the percentages of CD3+ HLA-DR+, of CD8+ CR3- and of CD57+ CD16- lymphocytes, and was greatly reduced after elimination of CD8+, of HLA-DR+ or of CD57+ cells. The median CTL activity seemed to increase from CDC group II to CDC group IV (Centers for Disease Control classification), but to return back to control levels in those patients with a history of opportunistic infections. NK function in HIV+ subjects was not significantly different from that in the blood donors. In seropositive patients, NK activity correlated positively with the percentages of both CD16+ CD57+ and of CD8+ CR3+ cells and was strongly diminished after elimination of CD16+ or of CD57+ cells. There was no significant change in NK function according to the clinical stage. The data show that circulating CD8+ HLA-DR+ CD57+ T cells in HIV+ subjects are activated cytotoxic T cells and point to progressive (over) activation of this T cell compartment until the onset of opportunistic infections.

Antigens, Surface↗

Schistosomicidal effects of Pavetta owariensis and Harrisonia abyssinica in mice infected with Schistosoma mansoni.

The schistosomicidal properties of ethanol and acetone extracts of Pavetta owariensis and an ethanol extract of Harrisonia abyssinica were assessed in mice infected with Schistosoma mansoni. Spleen weight, number of adult worms and eggs and size of liver granulomas were the main parameters studied. All P. owariensis extracts containing proanthocyanins were shown to cause a reduction in size of periovular granuloma formation in the liver. This effect was most pronounced with ethanol extracts of both "white bark" and "red bark" varieties of the plant. Acetone extracts of P. owariensis "red bark" variety, containing the highest concentration of proanthocyanins, caused a marked reduction of egg numbers in the liver and intestine whereas the ethanol extract of H. abyssinica proved to be inactive.

Animals↗

Schistosoma mansoni: impaired clearance of model immune complexes consisting of circulating anodic antigen and monoclonal IgG1 in infected mice.

The clearance of schistosome-specific model immune complexes (IC) consisting of circulating anodic antigen (CAA), a gut-associated excretory-secretory antigen, and radiolabeled monoclonal antibody (IgG1) was investigated in mice with a light and heavy Schistosoma mansoni infection and in noninfected control animals. The size analysis of the in vitro prepared and injected IC, as determined by density gradient centrifugation, revealed a wide peak at 11S. In infected animals the injected IC were cleared at a significantly lower rate than in control mice. This was attributed to a decreased uptake of IC by the liver in infected mice. In heavily infected mice, 30 min after injection of 11S IC, 8S, 11S, and greater than 11S IC were present in the serum, whereas only small 8S IC were detected in the serum of lightly infected animals and noninfected controls. Immune complexes were also present in the serum of heavily infected mice 30 min after injection of antibody and were detectable as 11S and greater than 11S IC. The importance of this study is twofold. First, these results show that schistosome-specific monoclonal antibodies can be used in the production of model immune complexes applicable in clearance studies. Second, our findings might be of importance when the possible pathogenicity of circulating IC in schistosomiasis is considered.

Animals↗

HLA studies of endemic African Kaposi's sarcoma patients and matched controls: no association with HLA-DR5.

In the search for a genetic factor involved in the etiology of Kaposi's sarcoma, several studies have recently focused on a significantly increased HLA determinant, DR5, as well as a decreased DR3, among patients with both the classical and the AIDS-related form of Kaposi's sarcoma. To test the consistency of this phenomenon, we analysed the frequencies of HLA immunogenetic markers in 23 histologically confirmed Kaposi's sarcoma patients from Central Africa, where this tumor is endemic, and a local sex- and tribe-matched control group. No definite association was observed for any of the HLA antigens, including DR5 and DR3. We were not able to support the hypothesis that the same HLA-associated immune susceptibility factors are involved in all types of Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗

ELISA HTLV retrovirus antibody reactivity associated with malaria and immune complexes in healthy Africans.

A serological survey of 250 outpatients in rural Zaire showed that the prevalence of antibody against HTLV-I, HTLV-II, and HTLV-III, as detected by enzyme-linked immunosorbent assay, correlated strongly with level of antibodies against Plasmodium falciparum. The age curve for the prevalence of antibody against these retroviruses and high titres of antibodies against P falciparum were similar. Tests with control sera obtained from HTLV-III seropositive homosexual men and American subjects repeatedly infected with malaria who had high antibody titres against P falciparum indicated that there was no cross-reactivity between P falciparum and these retroviruses. Immune-complex levels, but not IgG, IgM, or IgE levels, also correlated strongly with seropositivity in the ELISA HTLV-I and HTLV-III assay, although immune-complex-positive control samples were negative. Possible explanations include coincidental distribution paralleling malaria; similar mode of transmission; virus activation and/or enhanced antibody production due to the effect of malaria on the immune system; and false-positive reactivity in the ELISA assay due to cross-reactive antibodies or other unknown factors.

Adolescent↗

Endemic African Kaposi's sarcoma is not associated with immunodeficiency.

Twenty-seven histologically confirmed Kaposi sarcoma (KS) patients resident in the Kivu Lake area of eastern Zaire were examined for immune competence. Only KS cases of the endemic African type have been observed in this high-incidence area. The median duration of the symptoms was 6 years and ranged from 1 to 38 years. Forty-one controls matched for age, sex and tribe and unrelated to the KS patients were selected from the community. Thirteen additional controls were first-degree relatives of the KS patients. No evidence of immune suppression among KS patients was found and there were no significant differences in the immune status between KS patients and controls. Total lymphocytes, B and T cells, and OKT4+ and OKT8+ cells varied within the normal range. Grouping of the KS patients in categories according to duration and disease extent did not reveal significant differences in their immune status. The number of KS patients reacting positively in a skin test to 5 recall antigens and I mitogen was similar to that of controls, except in the case of candidin, to which a higher number of KS patients were negative. The serum levels of immunoglobulins, complement factors and circulating immune complexes were comparable in KS patients and controls. Indicators of inflammatory processes [white blood cells (WBC), complement-reactive protein (CRP)] were positive in 27% of the KS patients. The prevalence and mean titer of antibody against cytomegalovirus (CMV), Epstein-Barr virus (EBV), hepatitis B virus (HBV) and syphilis were similar in KS patients and in controls.

Acquired Immunodeficiency Syndrome↗

Seroepidemiology of HTLV-III antibodies in a remote population of eastern Zaire.

A human retrovirus--human T cell lymphotropic virus-III (HTLV-III)--has recently emerged as the probable cause of acquired immunodeficiency syndrome (AIDS). In May 1984, 250 outpatients at a hospital in a remote area of eastern Zaire were surveyed for AIDS type illnesses and the prevalence of antibodies against HTLV-III determined by an enzyme linked immunosorbent assay using disrupted whole HTLV-III virus as the antigen. No clinical cases of AIDS were diagnosed among these patients. Overall, 31 (12.4%) had clearly positive ratios (greater than or equal to 5.0) and a further 30 (12.0%) had borderline ratios (3.0- less than 5.0). Western blots of serum samples from subjects with antibodies yielded bands consistent with HTLV-III as found in American patients with AIDS and members of groups at risk of AIDS. The prevalence of antibody was highest in childhood (p = 0.02); among adults prevalence rose slightly with age. HTLV-III antibodies were more common among the uneducated (p = 0.006), agricultural workers (p = 0.03), and rural residents (p = 0.006), but the Western blot bands were generally weak in this group. By contrast, one urban resident had strong bands. The relatively high prevalence of antibodies among the rural poor in this area of Zaire suggests that HTLV-III or a closely related, cross reactive virus may be endemic in the region. A different natural history of infection, perhaps in childhood, may also explain the findings.

Acquired Immunodeficiency Syndrome↗