Brief Report: Effect of CMV and HIV Transcription on CD57 and PD-1 T-Cell Expression During Suppressive ART.

HIV-infected men who have sex with men are nearly universally coinfected with cytomegalovirus (CMV). In this study of 45 HIV-infected men who have sex with men virologically suppressed on ART, we found that presence of seminal CMV DNA shedding and higher levels of systemic cellular HIV RNA transcription were both independently associated with increased PD-1 expression on circulating CD4 T cells, but not with higher levels of senescent (CD57) T cells. In addition, greater HIV RNA transcription was associated with lower CD57 expression on CD8 T cells. Although causality cannot be inferred from this retrospective study, these results suggest that asymptomatic CMV replication and residual cellular HIV transcription may contribute to persistent immune dysregulation during suppressive ART.

[Morpho-functional reaction of spleen natural killer cells and macrophages to melatonin administration to the animals kept on different illumination regimens].

The aim this investigation was to study the changes in the numbers of spleen CD57+ and CD68+ cells (natural killer cells and macrophages respectively) after melatonin administration to the animals kept on different illumination regimens. The experimental animals were given melatonin in dose of 0.03 mg per day for 2 and 4 weeks under conditions of natural illumination or artificial darkening. Spleen paraffin sections were stained using immunohistochemical methods for detection of CD57+ and CD68+ cells. It was shown that long-term administration of melatonin under conditions of natural illumination had an immunosuppressive effect, that was manifested by the depopulation of the marginal zones, white pulp and all the zones of the red pulp, parenchyma loosening and denudation of the reticular stroma of the organ. However, long-term hormone administration under conditions of artificial darkening had an immunostimulatory effect as evidenced by the increased inflow of immunocompetent cells into the spleen, their migration from the white pulp into the marginal zones and emigration into peripheral blood flow, concomitant with the increase in the number of lymphoid nodules. The number of CD57+ and CD68+ cells was increased in splenic periarterial lymphoid sheaths and decreased in B-dependent zones of the organ.

HNK-1-Reactive oligosaccharide, sulfate-O-3GlcAbeta1-4Xylbeta1-MU, synthesized by cultured human colorectal cancer cells.

Human colorectal cancer cells were incubated with medium containing 4-methylumbelliferyl-beta-D-xyloside (Xyl-MU). The cells synthesized Xyl-MU-derivatives which were detected in the culture medium by gel-filtration high-performance liquid chromatography. These included a Xyl-MU-induced glycosaminoglycan and its biosynthetic intermediates, Galbeta1-4Xylbeta1-MU and Galbeta1-3Galbeta1-4Xylbeta1-MU, and other Xyl-MU-induced oligosaccharides, not related to Xyl-MU-induced glycosaminoglycan, were also synthesized. One of these oligosaccharides, sulfate-O-3GlcAbeta1-4Xylbeta1-MU, reacted with HNK-1, a mouse monoclonal antibody raised against human natural killer cells. Human neural cells and skin fibroblasts have also been reported to synthesize HNK-1-reactive sugar chains. Since HNK-1-reactive sugar chains are known to be involved in cell adhesion in the nervous system, the present results suggest that epithelium-derived colorectal cancer cells might also be able to utilize them in cell adhesion.

Intrahippocampal administration of an antibody against the HNK-1 carbohydrate impairs memory consolidation in an inhibitory learning task in mice.

Many cell adhesion molecules express the HNK-1 carbohydrate involved in formation and functioning of synapses. To assess its role in learning, we injected the monoclonal HNK-1 antibody or nonimmune IgG into the hippocampus of C57BL/6J mice 1 h after training in a step-down avoidance task. In animals treated with the HNK-1 antibody, latencies of step down in a recall session 48 h after injection did not change compared to training values and were significantly shorter versus IgG-treated controls, which acquired the task normally. Similar differences between the two treatments were also observed after a stronger training protocol in a step-down avoidance paradigm. The HNK-1 antibody was effective only when injected 1 h, but not 48 h after training, thus affecting memory consolidation but not memory recall itself. The HNK-1 antibody impaired memory also in tenascin-R knock-out mice, indicating that extracellular matrix molecule tenascin-R, one of the carriers of the HNK-1epitope in the hippocampus, does not mediate the function of the HNK-1 carbohydrate in this task. Our observations show that the HNK-1 carbohydrate is critically involved in memory consolidation in hippocampus-dependent learning in mammals.

Effects of occupational metallic mercury vapour exposure on suppressor-inducer (CD4+CD45RA+) T lymphocytes and CD57+CD16+ natural killer cells.

OBJECTIVES: To examine the effects of metallic mercury vapour on the cellular and humoral immune system. METHODS: We measured T lymphocyte and natural killer (NK) cell subpopulations, B lymphocytes, and serum immunoglobulins (i.e. IgG, IgA and IgM) together with total T (CD3 +) lymphocytes and total lymphocytes in blood samples from 20 male, fluorescent-lamp makers (mercury workers) and the same number of gender-, age- and smoking-matched controls. Urinary concentrations of inorganic mercury (UHg) in the 20 workers ranged from 1.8 to 163.5 (mean 44.8) microg/l. They had been exposed to mercury vapour for 4 to 62 (mean 31) months. RESULTS: Numbers of CD4+CD45RA+ (suppressor-inducer) T lymphocytes and total CD4+ T lymphocytes in the mercury workers were significantly smaller than those in the controls (paired-sample t-test, P < 0.01). The number of CD57+CD16+ NK cells was inversely correlated with UHg. CONCLUSION: It is suggested that numbers of CD4+CD45RA+ T lymphocytes and CD57+CD16+ NK cells are inversely affected by exposure to metallic mercury vapour in workers, with an average urinary inorganic mercury concentration of 45 microg/l being found.

Increase in CD57 + CD16-lymphocytes in workers exposed to benzidine and beta-naphthylamine: assessment of natural killer cell subpopulations.

Previously, we found a decrease in CD4 + CD45RA + T lymphocytes in workers exposed to the aromatic amines (AAs) [benzidine (BZ) and beta naphthylamine (BNA)]. For further investigation of the effects of AAs on lymphocyte subpopulations, we measured natural killer (NK) cell subpopulations using two-color staining with anti-Leu7 (CD57) and anti-Leu11 (CD16) monoclonal antibodies in peripheral blood in 78 male dyestuff workers. The workers had been exposed to AAs before 1972 at a chemical plant, either in the production of AAs (40 workers, high-exposure group) or in other work that involved handling dyestuffs (38 workers, low-exposure group). The controls were 30 "healthy" male volunteers without a history of occupational exposure to AAs or hazardous chemicals. The number of CD57 + CD16- cells in the high-exposure group was significantly higher than that in the controls (P < 0.01, analysis of covariance with age as a covariate). No significant differences were found in CD57 + CD16-, CD57 + CD16+ and CD57- CD16 + NK cells between the low-exposure group and the controls. It is suggested that a decrease in the number of CD4+ T lymphocytes following exposure to AAs might be compensated by the increase in CD57 + CD16- cells, i.e. circulating peripheral lymphocytes with poor NK cell activity.