Human immunodeficiency virus infection down-regulates HLA class II expression and induces differentiation in promonocytic U937 cells.

We studied the effect of human immunodeficiency virus (HIV) infection on the surface-marker expression of the human promonocytic cell line U937. U937 cells persistently produced HIV as detected by reverse transcriptase activity in culture supernatant. Expression of HLA class II antigens on U937/HIV cells was decreased 2- to 10-fold, depending on the Mab used. Class II expression of U937/HIV cells increased approximately two-fold by treatment with r-interferon-gamma. Whereas noninfected U937 cells expressed moderate amounts of lymphocyte function-associated antigen-1 (LFA-1) (CD11a) and minimal amounts of the C3bi receptor (CD11b) and p150/95 (CD11c), U937/HIV cells expressed moderate amounts of C3bi receptor and p150/95 and showed elevated expression of LFA-1 alpha (CD11a) and -beta (CD18) chains. Expression of these adhesion molecules resulted in strongly enhanced phorbolester-induced aggregation of U937/HIV cells compared with the noninfected U937 cells. In addition, almost all U937/HIV cells, but not noninfected U937 cells, intensely stained for cytoplasmic nonspecific esterase activity. The effects of HIV infection on U937 cells strikingly resemble the effects of differentiation-inducing agents, such as PMA and DMSO, on the U937 phenotype. Our finding suggests that HIV infection, apart from down regulating class II expression, induces differentiation of U937 cells.

Immunological abnormalities in human immunodeficiency virus (HIV)-infected asymptomatic homosexual men. HIV affects the immune system before CD4+ T helper cell depletion occurs.

To investigate the effect of persistent HIV infection on the immune system, we studied leukocyte functions in 14 asymptomatic homosexual men (CDC group II/III) who were at least two years seropositive, but who still had normal numbers of circulating CD4+ T cells. Compared with age-matched heterosexual men and HIV-negative homosexual men, the CD4+ and CD8+ T cells from seropositive men showed decreased proliferation to anti-CD3 monoclonal antibody and decreased CD4+ T-helper activity on PWM-driven differentiation of normal donor B cells. Monocytes of HIV-infected homosexual men showed decreased accessory function on normal T cell proliferation induced by CD3 monoclonal antibody. The most striking defect in leukocyte functional activities was observed in the B cells of HIV-infected men. B cells of 13 out of 14 seropositive men failed to produce Ig in response to PWM in the presence of adequate allogeneic T-helper activity. These findings suggest that HIV induces severe immunological abnormalities in T cells, B cells, and antigen-presenting cells early in infection before CD4+ T cell numbers start to decline. Impaired immunological function in subclinically HIV-infected patients may have clinical implications for vaccination strategies, in particular the use of live vaccines in groups with a high prevalence of HIV seropositivity.

Plasma eicosanoids and platelet aggregation as parameters to monitor tumor patients. A study in 12 healthy subjects to obtain baseline levels.

Plasma levels of the eicosanoids PGE2, 6k-PGF1 alpha and TXB2 as well as platelet aggregation were determined in 12 healthy subjects, aging 23-50. It was our assumption that the parameters could be of use to monitor cancer patients, provided that the results of the determinations could be well reproduced and that the variation within a healthy population was small. In a group of laboratory employees (6 males and 6 females) blood samples were taken, 3 times, with a 2 week interval, under controlled conditions. Drug ingestion was recorded, and taken into account for the evaluation. The ranges of plasma eicosanoid, and of in vitro platelet aggregation values were large. The variation in both parameters was in large part due to intra-individual variation (based on the different values obtained in one subject). In part however, the variation could be traced to ingestion of non steroidal anti inflammatory drugs (NSAIDs). The following abbreviations were used: NSAID = non steroidal anti inflammatory drug, PGE2 = prostaglandin E2, 6k-PGF1 alpha = 6-ketoprostaglandin-F1 alpha, TXB2 = thromboxane B2, TXA2 = thromboxane A2, PGI2 = prostaglandin I2 = prostacyclin, RIA = radio immuno assay, ADP = adenosine diphosphate.

[Promotion Program Health Survey (SGO). IX. Evaluation of the program section 'Toxicology']. / Het Stimuleringsprogramma Gezondheidsonderzoek (SGO). IX. Evaluatie van het deelprogramma 'Toxicologie'.

As a part of the SGO Health Research Promotion Programme, in collaboration with the Toxicological Research Stimulation Programme, a research programme in the field of toxicology was realized. The study ran from 1990 to 1994 (4 years) and comprised animal and clinical research into the possible adverse effects of exposure of the foetus and the neonate to polychlorobiphenyls (PCBs), polychlorodibenzoparadioxins and polychlorodibenzofurans via the placenta and maternal milk. The clinical studies in neonates revealed a slight alteration of the thyroid metabolism (still within normal limits) after increased exposure to dioxides and PCB (as measured in maternal plasma, cord plasma and maternal milk), while slight neurological abnormalities without clinical relevance were also observed. It is concluded from these study results that there are no grounds to advise against breast feeding.

[The Stimulation Program Health Research. X. Evaluation of the program section 'Psychogeriatrics']. / Het Stimuleringsprogramma Gezondheidsonderzoek (SGO). X. Evaluatie van het deelprogramma 'Psychogeriatrie'.

In the programme section 'Psychogeriatrics' of the SGO Health Research Promotion Programme a longitudinal study was carried out in Amsterdam from 1989 until 1994, concerning the course of mild cognitive decline in elderly people (the AMSTEL project). The scientific aims were the development of diagnostical instruments for the early diagnosis of dementia, the development of criteria which predict the course of mild cognitive impairment and the expansion of knowledge on the relationship between somatic and psychiatric pathology and dementia. The programme also had aims regarding medical education and patient care. The results include the following: in order to diagnose dementia in general practice questions regarding orientation and short-term memory are helpful. Risk factors for cognitive deterioration in elderly people include hippocampal atrophy on the MRI scan, a low level of education and subjective complaints regarding memory. Subjective complaints regarding memory are not primarily caused by a depressive mood, as is often thought, but are important as correct self-observations of cognitive deterioration, and go with an increased risk of developing dementia. Besides the AMSTEL project a feasibility study was carried out concerning a psychogeriatric case register in Amsterdam.

Decreased accessory cell function by human monocytic cells after infection with HIV.

We studied the effect of HIV infection on the human monocytic cell line U937. The cell line was infected with cellfree HIV, strain HTLV-IIIB. After 3 wk, a high reverse transcriptase activity was continuously detected in the supernatant of the cell line. Neither cytopathic effects nor changes in cell growth were observed. After infection, accessory cell function on T cell proliferation induced by anti-CD3 mAb of both IgG1 and IgG2a subclasses and Con A was tested. Accessory cell function provided by U937 cells started to decline 3 wk after inoculation with HIV. This correlated with detectable reverse transcriptase activity. The remaining accessory cell capacity varied between 10 and 60% of accessory cell function mediated by noninfected U937 cells. It was excluded that decreased FcR expression on U937/HIV cells contributed to the accessory cell defect in the anti-CD3-driven system. IL-2R expression on T cells, cocultivated with U937/HIV and anti-CD3, was minimal. The accessory cell defect could only be partly overcome by addition of rIL-2 or IL-1. Addition of high titer (10(4) TCID50) HIV or U937/HIV cells did not affect T cell proliferation, which rules out that the observed inhibition is caused by HIV infection of T cells or suppressive effects of U937/HIV cells. These results suggest that infection of APC may contribute to the induction of immunologic abnormalities in early HIV infection. Thus, monocytes/macrophages may not only serve as a reservoir for the dissemination of HIV, but may be an important target cell through which the immune system is affected.