Peter Grob

Genotypic, phenotypic and functional analysis of CD4+CD7+ and CD4+CD7- T lymphocyte subsets in Sézary syndrome

Abstract  The expansion of CD4 + CD7 – T cells in the peripheral blood of Sézary syndrome (SS) is well known. It remains unclear whether this population contains the dominant T cell clone. Peripheral blood mononuclear cells (PBMC) of five SS patients were sorted by fluorescence-activated cell sorting into CD4 + CD7 – and CD4 + CD7 + populations. These populations were analysed separately for clonality of the T cell receptor γ chain (TCR-γ) by PCR-DGGE. The cytokine profile of both populations was investigated by RT-PCR ELISA for IFN-γ, IL-2, IL-4, IL-5, IL-10, IL-13 and IL-15. In three other patients with known Vβ-usage, the dominant T cell clones were phenotypically characterized by double staining. PCR-DGGE of TCR-γ demonstrated that all patients had a clonal population in their blood and that this population was present in CD4 + CD7 – and CD4 + CD7 + populations. Concerning mRNA cytokine transcription, the two populations did not show any consistent differences. In three patients with identified clones (Vβ 3.1, 5.3 and 6.7), double staining revealed positivity for CD2, CD3, CD4, CD5, CD45RO and CD7 in a significant proportion (at least 35%). We conclude that the CD4 + CD7 – population does not represent the dominant T cell clone in patients with SS. An increase in this population of PBMC in SS might account for deviations in the T cell functions of the patients.

Prevention of hepatitis C virus infection

In spite of advances made in our understanding of the biology of the hepatitis C virus (HCV), the epidemiology and natural history of HCV infection, and the treatment of chronic hepatitis C, the development and worldwide implementation of a comprehensive prevention and control strategy remains necessary. A World Health Organization informal consultation with the Viral Hepatitis Prevention Board was convened and met in Geneva, Switzerland, 13–14 May 2002, to review epidemiological and public health aspects of HCV infection, and the various prevention and control strategies that are currently in place. Based on the presentations and discussions, a number of specific recommendations were made, which should be considered in conjunction with previously published recommendations.

The use of anti-T-cell receptor-Vβ antibodies for the estimation of treatment success and phenotypic characterization of clonal T-cell populations in cutaneous T-cell lymphomas

Summary. Sézary syndrome and Mycosis fungoides are the most common forms of cutaneous T‐cell lymphomas. To assess the response to different therapies especially in Sézary syndrome, it is helpful to monitor the percentage of circulating tumour cells in the blood. The use of T‐cell receptor (TCR)‐Vβ specific monoclonal antibodies provides a suitable tool for detecting Sézary cells. In this study, we analysed the levels of clonal CD4+Vβ+ cells of seven patients with various treatment modalities using flow cytometry and investigated the immunophenotype of the clonal cells by double staining with a panel of antibodies recognizing lymphatic surface markers. Additionally, a polymerase chain reaction‐denaturing gradient gel electrophoresis assay was performed on clonal CD4+Vβ2+ cells, showing that these cells carry a Vγ10/11, JγP1/2 TCR rearrangement. Follow‐up studies revealed close association of the Vβ+ clone developmentwith the clinical response to different therapiesinsixpatients. Intwo cases, the CD4+Vβ+ cells decreased accompanied by partial regression or even complete remission. In four cases, a stable or increasing clonal CD4+Vβ+ population reflected well a stable or progressing course of the disease. Double staining of Vβ+ cells revealed the following pattern, CD3+, CD5+, CD7+, CD28+, CD80–, CD86+ and human leucocyte antigen (HLA) class I+. In contrast, HLA‐DR was heterogeneously expressed. We conclude that identification and monitoring of CD4+Vβ+ clonal T cells by fluorescence‐activated cell sorting with double staining is a suitable method to assess clinical responses to different therapies.

Lymphokines and the brain

ConclusionThere seems little doubt that extensive communications between the immune systems and the central nervous system do exist. Besides direct contacts between the cells of the two compartments, soluble factors are clearly involved. The pathways elaborated so far mainly describe the fever and possibly also sleep-inducing effects of macrophage-derived interleukin-1, the astrocytes as antigen presenting cells and producers of interleukin-1 like factors, and the neuroimmune-endocrine interactions. By continuing these studies, it will be possible to provide significant proof to unlock the paradigm of the brains as an immunogically priviledged site.

Hepatitis B: virus, pathogenesis and treatment

The hepatitis B virus (HBV) is a coated, incompletely double-stranded DNA virus with some outstanding features. (1) All three coat proteins of HBV contain HBsAg, which is highly immunogenic inducing anti-HBs. These antibodies are protective for HBV outer cells (humoural immunity). Structural viral proteins induce specific T-lymphocytes, which are able to eliminate HBV-infected cells (cytotoxic T-cells; cellular immunity). (2) Intracellular HBV primarily causes little or no damage (non-cytopathogenic), which is an excellent strategy of viral survival. However, viral oligo-peptides of 8-15 amino acids are loaded on host cell MHC-class 1 molecules and are transported to the cell surface. Thus, HBV-specific T-lymphocytes are able to detect infected cells and destroy them, an ingenious defence strategy. However, this cell deletion triggered by inflammation cells may result in acute hepatitis. If HBV is not eliminated, a delicate balance between viral replication and immunodefence prevails which may lead to chronic hepatitis and liver cirrhosis. (3) In chronically infected cells HBV may become partly cytopathogenic--a process still poorly understood--and the viral DNA may integrate into the host cell DNA (through a viral transcriptase). If integration leads to activation of crucial host genes a hepatocellular carcinoma results. These outstanding features are responsible for the highly variable course of HBV infection and its final outcome, e.g. when the load of HBV-infected cells is still low at the time when an efficient immune defence starts, the infection is self-limited and asymptomatic, and immunity results. When there is no immune defence or a defective immune defence (immune tolerance of new-borns or immunosuppressed individuals) the HBV infection very often becomes chronic. In these cases, no acute hepatitis occurs, but hepatocellular carcinoma may result. Treatment with Interferon has become accepted, resulting in up to 30 to 40% of cases in the elimination of the virus. However, treatment is laborious and expensive, and the mechanism of action is still poorly understood (anti-viral and/or immune-modulating).

Switzerland, HIV and the power of pragmatism: Lessons for drug policy development

Switzerland in the 1980s was an epicentre of HIV as open drug injection became part of the urban scene, especially in Zurich. Cracks appeared in Switzerlands long commitment to policing as the main drug-control strategy as law enforcement was unable to contain the health and social consequences of the rapid spread of drug injection. In the early stages of the epidemic, the pioneering health care providers who brought technically illegal harm reduction services into the open drug scene in Zurich helped open the exploration at the federal level of more balanced drug policy. Carefully evaluated pilot experiences in low-threshold methadone, needle exchange, and eventually heroin-assisted therapy yielded evidence of significant HIV prevention and crime reduction that was convincing not only to policy-makers but also to a skeptical Swiss public. Whilst not all countries have Switzerlands resource base, the Swiss experience still holds many useful lessons for establishing evidence-based policy on illicit drugs.

Introduction to epidemiology and risk of hepatitis B

The most important modes of transmission of hepatitis B virus (HBV) are sexual, needle stick (both accidental or through intravenous drug use), blood transfusion or from mothers to newborns. The outcome of HBV infection mainly depends on the immune response of the host but is also influenced by the capability of the virus to escape defence mechanisms by integration into the genome of the hosts hepatocytes. These factors affect whether HBV infection leads to acute hepatitis or remains asymptomatic, whether the infection resolves to immunity or becomes chronic and whether chronic clinical sequellae such as chronic hepatitis, liver cirrhosis or hepatocellular carcinoma develop. The epidemiological status of a given country with regard to HBV depends on socioeconomic factors, the proportion of individuals with risky life styles, the pre-existing prevalence of HBV, the vaccine programme available and compliance to hygienic measures.

Transfer Factor Treatment of Patients with Multiple Sclerosis

In five patients with definite multiple sclerosis and lack of cell‐mediated immunity to measles and parainfluenza virus antigens, various immunological parameter were studied before and during transfer factor treatment. The study showed that cell‐mediated immunity to measles virus antigen, as evaluated by the leukocyte migration agarose test, could temporarily be restored, using repeated injections of transfer factor pooled from unselected, normal blood donors.

TRANSFER FACTOR TREATMENT OF PATIENTS WITH MULTIPLE SCLEROSIS: II. Immunological parameters in a long-term clinical trial

Publisher Summary This chapter describes results of experiments undertaken to study transfer factor (TF) treatment of patients with multiple sclerosis (MS). The study described the changes observed in the clinical and immunological parameters in 12 MS patients treated for more than a year with repeated injections of TF. It is stated that the evaluation of immunological capabilities is based on in vitro testings only, because repeated use of skin tests per se may introduce changes in reactivity. Clinical evaluation was done monthly and the results were expressed as a total neurological disability score. No side effects of the treatment were observed, except for local pain at the side of injection. The report points out that in one case, the team observed however, local inflammation. The tests showed that after the initial treatment period a significant decrease in percentages of B-cells were observed, but these values return to normal levels within the treatment period. The results showed that only minor changes in the unspecific immunological parameters were observed in the study.

The European Public Health Association

The European Public Health Association (EUPHA) was founded in 1992 and represents 11 European countries. Its goals include encouraging collaboration in furthering European public health through research, education and action based on sound scientific grounds. It provides an opportunity for those interested in public health to meet and exchange information, both through an annual conference and a quarterly scientific journal. EUPHA is delighted to be represented on the Viral Hepatitis Prevention Board and supports the aims of the Congress.