Factor VIII and transmissible spongiform encephalopathy: the case for safety

Haemophilia A is the most common inherited bleeding disorder, caused by a deficiency in coagulation factor VIII (FVIII). Current treatment of haemophilia A is based on repeated infusions of plasma-derived FVIII concentrate or of recombinant FVIII, which may be exposed to plasma-derived material of human or animal origin used in its tissue culture production process. We review epidemiological and experimental studies relevant to blood infectivity in the transmissible spongiform encephalopathies (TSEs, or 'prion' diseases), and evaluate the hypothetical risk of TSE transmission through treatment with plasma-derived or recombinant FVIII.     

Production of interferons by bovine and ovine cell lines infected with Theileria annulata or Theileria parva

Three bovine cell lines and four ovine cell lines infected with Theileria parva or Theileria annulata were examined for the production of interferon (IFN). Biologically active IFN was detected in the tissue culture supernatants of four of the cell lines. Only one, a bovine cell line infected with T. parva, produced IFN-gamma as measured by specific neutralization with a monoclonal antibody to bovine IFN-gamma. This observation was confirmed by analysing RNA from the cell lines on Northern blots using an IFN-gamma cDNA probe. The other three cell lines which produced IFN were infected with T. annulata. The IFN produced by those lines was not IFN-gamma.     

Human T-lymphocyte growth factor: regulation of growth and function of T lymphocytes

The discovery of T-cell growth factor (TCGF) has made it possible to now routinely grow in tissue culture normal and neoplastic human T cells for long periods and in large amounts. TCGF has been recently purified. It is a small protein released by a subset of mature T cells following lectin-antigen activation, which in turn acts upon other T- cell subsets that have developed specific receptors for TCGF after lectin-antigen stimulation. Thus, release of TCGF and development of receptors for it appear to be obligatory for the clonal expansion of all activated T cells. Unlike normal T cells, neoplastic T cells respond directly to TCGF, requiring no prior in vitro lectin-antigen activation. This has led to the development of several new cell lines from patients with T-cell leukemias and lymphomas. In some cases, these cells become independent of exogenous TCGF by producing their own growth factor, implying a role for TCGF in the continuous proliferation of these cells. These developments necessitate a reevaluation of some concepts of immunoregulation of T-cell activities in terms of production and response to TCGF. In addition, this information has clinical implications. Recent results have shown that a major defect of the athymic nude mouse is the inability to produce TCGF and that some immunosuppressive agents, such as glucocorticosteroids and cyclosporin- A, exert their effects on T cells by disrupting the TCGF-T-cell interaction. Some human immune deficiencies might be due to a failure to respond to or to produce TCGF, which in some cases might be corrected by exogenous TCGF.     

Systemic release of a mast cell proteinase following nematode infections in sheep

An enzyme-linked immunosorbent assay (ELISA) for sheep mast cell proteinase (SMCP) has been developed. Concentrations of SMCP in homogenates of abomasal tissue from parasite-immune sheep (341 micrograms SMCP/g tissues) were raised when compared to those in normal (non-infected) abomasa (0.145 micrograms SMCP/g tissue). SMCP was not detected in sera from normal animals challenged with Haemonchus contortus but was present (less than 1.0 ng SMCP/ml) in sera from 8/11 immune sheep 2 h after intra-abomasal challenge with 1 x 10(6) exsheathed Haemonchus larvae. In two further experiments, the SMCP response in gastric lymph was monitored after homologous larval challenge in sheep immune to Ostertagia circumcincta and in normal controls. SMCP (less than 1.4 ng SMCP/ml) was detected in lymph from 2/3 and 4/5 immune animals between 1 and 4 days post-challenge with 50,000 larvae, but not from normal animals. SMCP was not detected in lymph from immune animals following challenge with 1000 Ostertagia larvae. The relatively low concentrations of SMCP in blood and lymph reflect the presence of proteinase inhibitor(s) which interfered with the ELISA.     

Invasion of erythrocytes in vitro by Plasmodium falciparum can be inhibited by monoclonal antibody directed against an S antigen

A monoclonal antibody has been produced which binds to the heat stable S antigen present in the FCQ-27/PNG isolate of Plasmodium falciparum. This monoclonal antibody also inhibits the invasion in vitro of erythrocytes by malarial merozoites thus demonstrating that the S antigens of Plasmodium falciparum may be a target of protective immune responses.     

Creutzfeldt-Jakob disease: reflections on the risk from blood product therapy

Abstract  Creutzfeldt-Jakob disease (CJD) was first described as a clinical entity in the 1920s, first transmitted experimentally in 1968, and first transmitted iatrogenically in 1972 (corneal transplant). Numerous experimental studies in rodents, sheep and primates have since revealed very low levels of infectivity in blood (about 1/100 000th the level in brain tissue) that can appear as early as half-way through the incubation period, with 5–10 fold higher concentrations in leucocytes than plasma. Transfused blood from individuals incubating the variant form of CJD has transmitted infection to four recipients in the United Kingdom, and several dozen other recipients remain at risk. Plasma and plasma proteins have not been implicated in any transmissions, and no instance of transmission from the blood of individuals incubating other forms of CJD has been recognized. Strategies to prevent iatrogenic transmissions include low-risk sourcing, leucodepletion, and a variety of infectivity-reducing plasma processing steps; screening tests to detect infection in preclinical donors are under development.     

Cellular mechanisms involved in recovery from acute malaria in Gambian children

This paper reports the results of in vitro experiments which attempt to elucidate the mechanisms whereby Gambian children control acute infections of Plasmodium falciparum. It was shown initially that mononuclear cells from children with acute malaria, in the presence of specific antibody, caused a marked reduction in in vitro parasite growth. IgM antibodies appeared to be considerably more effective than IgG. T or B lymphocytes were ineffective in the system; adherent cells alone had some effect, but much less than the unfractionated cell population. Adherent cells were however fully effective after exposure to supernatants from T cells activated either non-specifically by phytohaemagglutinin (PHA), or specifically by P. falciparum antigens. Depression of parasite growth was also observed, independent of anti-malarial antibody. This was achieved when adherent cells from healthy Europeans, as well as those from infected children, were exposed to the supernatants from previously stimulated T cells before adding to the culture. Furthermore, intra-erythrocytic parasite death occurred after a short exposure to the supernatants of 'activated' adherent cells from both infected children and Europeans.