Differential effect of agonistic anti-CD40 on human mature and immature dendritic cells: the Janus face of anti-CD40

Agonistic monoclonal antibodies to CD40 (CD40 mAbs) have a puzzling dual therapeutic effect in experimental animal models. CD40 mAbs induce tumor regression by potentiating antitumoral T-cell responses, yet they also have immunosuppressive activity in chronic autoimmune inflammatory processes. CD40 mAbs are thought to act on antigen presentation by dendritic cells (DCs) to T cells. DCs can be distinguished as either immature or mature by their phenotype and their ability to generate an effective T-cell response. Here we found that, on human cells, although anti-CD40 led immature DCs to mature and became immunogenic, it also reduced the capacity of lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF-alpha)-matured DCs to generate a specific CD4 T-cell response. This inhibitory effect was related to rapid and selective apoptosis of mature DCs. Anti-CD40-mediated apoptosis was due to an indirect mechanism involving cooperation with the death domain-associated receptor Fas, leading to activation of Fas-associated death domain protein (FADD) and caspase-8. On human cells, CD40 activation by such agonists could, therefore, trigger immune responses to antigens presented by immature DCs, which are otherwise nonimmunogenic, by inducing maturation. On the other hand, anti-CD40 mAbs, by rapidly inducing apoptosis, may reduce the capacity of inflammatory signal-matured immunogenic DCs to generate an effective T-cell response. These results call for caution in CD40 mAb-based immunotherapy strategies.     

Evaluation of iron, zinc, and copper levels in pterygium tissue

Purpose  

To determine the concentration of the trace elements iron, copper, and zinc in pterygium tissue and healthy conjunctiva tissue and to investigate the involvement of these elements in pterygium etiopathogenesis.     

Some Heavy Metals Accumulation in Tissues in <Emphasis Type="Italic">Capoeta umbla</Emphasis> (Heckel, 1843) from Uzuncayir Dam Lake (Tunceli,Turkey)

Concentrations of metals were determined in the gills, liver, kidney, heart and muscle in Capoeta umbla caught from six stations from the Munzur River system. Metal concentrations in the tissues tended to vary significantly among stations (p < 0.05). Liver (Cu, 10.10 ± 0.23–23.03 ± 9.37 ppm; Zn, 14.67 ± 3.01–21.82 ± 2.39 ppm; Cd, 18.04 ± 4.56–52.69 ± 10.65 ppb and Fe, 28.87 ± 6.78–115.11 ± 34.87 ppm) and kidney (Cu, 1.80 ± 0.25–3.70 ± 0.62 ppm; Zn, 20.81 ± 0.37–29.36 ± 0.70 ppm; Cd, 132.06 ± 5.29–639.51 ± 20.14 ppb and Fe, 24.40 ± 1.98–59.39 ± 1.97 ppm) tissues showed higher metal concentrations than other tissues. It seems that metal contamination in the river is too high for the health of fish and the people who eat them. The geographical locations of catch, season, nature of diet, and the size of fish used for analyses might lead to different metal concentration in the same fish species.     

Hepatitis B virus e antigen (HBeAg) may have a negative effect on dendritic cell generation

Hepatitis B virus (HBV) continues to be a serious worldwide health problem despite the use of protective HBV vaccines and therapeutic regimens against chronic HBV infection. Chronic HBV patients cannot induce sufficient immune responses against the virus. HBV and its antigens are believed to suppress immune responses during chronic infection. Hence, studying the role of HBV in immune suppression is very important for the development of alternative therapeutic strategies for HBV infections.     

Treatment of acne with intermittent and conventional isotretinoin: a randomized,controlled multicenter study

Oral isotretinoin is the most effective choice in the treatment of severe acne. Application of isotretionin to acne has been expanded to treat those patients with less severe but scarring acne who are responding unsatisfactorily to conventional therapies. However, its use is associated with many side effects, some of which can result in very disastrous consequences. Data related with intermittent isotretinoin therapy is still limited. Our aim was to asses the efficacy and tolerability of two different intermittent isotretinoin courses and compare them with conventional isotretinoin treatment. In this multicenter and controlled study, 66 patients with moderate to severe cases were randomized to receive either isotretionin for the first 10 days of each month for 6 months (group 1), or each day in the first month, afterwards the first 10 days of each month for 5 months (group 2) or daily for 6 months (group 3). The drug dosage was 0.5 mg/kg/day in all groups. Patients were followed-up for 12 months. Efficacy values were evaluable for 22 patients in group 1, 19 patients in group 2, and 19 patients in group 3. Acne scores in each group were significantly lower at the end of treatment and follow-up periods (P < 0.001). When patients were evaluated separately as moderate (n = 31) and severe (n = 29), no statistically significant differences were obtained among the treatment protocols in patients with moderate acne. However, there was a significant difference between groups 1 and 3 to the response of the treatments in severe acne patients at the end of follow-up period (P = 0.013). The frequency and severity of isotretionin-related side effects were found to be lower in groups 1 and 2 compared with group 3. Intermittent isotretinoin may represent an effective alternative treatment, especially in moderate acne with a low incidence and severity of side effects. The intermittent isotretinoin can be recommended in those patients not tolerating the classical dosage.     

Critical role of JC virus-specific CD4 T-cell responses in preventing progressive multifocal leukoencephalopathy

BACKGROUND: JC virus (JCV) is ubiquitous among the general population. However, only individuals with severely impaired immunity, mainly AIDS patients, develop progressive multifocal leukoencephalopathy (PML). Here, we examined the role of specific CD4 T cells in the control of JCV infection. METHODS AND DESIGN: JCV-specific CD4 T-cell responses were investigated by assaying peripheral blood mononuclear cell proliferation in response to the purified virus. Four groups of individuals without PML were examined: 14 HIV-seronegative healthy donors and 25 HIV-infected patients without PML, separated into urinary JCV excretors (active infection) and non-excretors, according to JCV PCR on urine. Two groups of patients with PML were also studied: 14 HIV-infected patients with active PML; and 10 PML survivors on effective and prolonged antiretroviral therapy. All of the patients were PCR-positive for JCV in the cerebrospinal fluid at the time of diagnosis of PML. RESULTS: No significant anti-JCV CD4 T-cell proliferation was found in any of the non-excretors tested. All nine healthy donors and seven of the 13 non-PML HIV-infected patients with urinary JCV excretion had positive JCV-specific CD4 T-cell responses. No significant response was found in the 14 patients with active PML, while nine of the 10 PML survivors had positive responses. Restoration of JCV-specific CD4 T-cell responses was associated with JCV clearance from the cerebrospinal fluid. CONCLUSION: JCV-specific CD4 T-cell responses appear to play a critical role in the control of JCV infection, preventing PML development. Such responses can be restored in PML survivors following effective and prolonged antiretroviral therapy.     

Restoration of the immune system with anti-retroviral therapy

Clinical benefits of highly active anti-retroviral treatments (HAART) are increasingly evidenced by resolving opportunistic infections and malignancies, as well as declining hospitalization and mortality rates [1]. This suggests that potent and sustained suppression of viral replication, at least to some extent, is associated with reconstitution of the immune system even in adult patients treated at advanced stages of the disease. Increased susceptibility to opportunistic infections and tumors mainly results from the loss of memory CD4+ T cell reactivity against recall antigens which is an early event in HIV disease progression. Primary responses of naive CD4+ T cells against new pathogens are suppressed even earlier in the course of HIV disease, and the progressive depletion in naive CD4+ T cells reflects profound alterations in T cell regeneration capacities. Previous studies revealed that monotherapy with ritonavir, a protease inhibitor, resulted in a slight improvement in memory CD4+ T cell responses to recall Ags only when detectable prior to onset of therapy, suggesting that the loss of CD4+ T cell reactivity might be irreversible at advanced stages of the disease [2]. In contrast our group demonstrated more recently that restoration in CD4+ T cell reactivity to specific antigens was feasible when HAART was administered in progressors [3]. Here we address some of the questions raised by immune restoration with HAART when administered at advanced stages of the disease.     

Metal bioaccumulation in selected tissues of barb (Barbus sp.) and common carp (Cyprinus carpio,Linnaeus 1758) from the Keban Dam Lake,Turkey

Abstract

The aquatic life has been negatively influenced by harmful effects of environmental toxic elements, including heavy metals. The elevated concentrations of metals may be harmful for aquatic animals and human health. Herein, the present study deals with assessment of the bioavailability of metals [cadmium (Cd), chrome (Cr), copper (Cu), zinc (Zn), iron (Fe), lead (Pb), manganese (Mn), mercury (Hg), nickel (Ni), and selenium (Se)] in organs such as muscle, gills, liver, kidney, and gonad of the commercially consumed Barbus sp. and Cyprinus carpio (Linnaeus, 1758) collected from Keban Dam Lake, eastern Turkey. The fish were captured from four different stations of Keban Dam Lake. Our results indicated that Fe and Zn concentrations were the highest in all tissues of two fish species while Cd concentrations were the lowest levels. In addition, detected metals accumulated in the muscle of common carp at higher levels compared to Barbus sp. The results from the present study also demonstrated significant variations and considerable differences in the concentrations of all 10 elements between the four stations and different fish tissues. Overall, the concentrations of detected metals in the muscle were many folds higher than the permissible level prescribed by some national and international legislation, which raises health risk concerns.