A clonal culture system demonstrates that IL-4 induces a subpopulation of noncytolytic T cells with low CD8, perforin, and granzyme expression

Immune deviation of cytolytic T cell function, induced by type 2 cytokines like IL-4, is an attractive concept to explain failure of the immune system in some diseases. However, this concept is challenged by previous conflicting results on whether type 2 cytokine-producing CD8(+) T cells are cytolytic. Therefore, we have analyzed the relationship between cytolytic activity and cytokine production among large numbers of primary CD8(+) T cell clones. Single murine CD8(+) T cells of naive phenotype were activated at high efficiency with immobilized Abs to CD3, CD8, and CD11a in the presence of IL-2 (neutral conditions) or IL-2, IL-4, and anti-IFN-gamma Ab (type 2-polarizing conditions) for 8-9 days. Under neutral conditions, most clones produced IFN-gamma without IL-4 and were cytolytic. Under type 2-polarizing conditions, most clones produced IFN-gamma and IL-4 but displayed variable cytolytic activity and CD8 expression. Separation on the basis of surface CD8 levels revealed that, compared with CD8(high) cells from the same cultures, CD8(low) cells were poorly cytolytic and expressed low levels of perforin mRNA and protein and granzyme A, B, and C mRNA. A similar, smaller population of noncytolytic CD8(low) cells was identified among CD8(low) T cells activated in mixed lymphocyte reaction with IL-4. Variable efficiency of generation of the noncytolytic cells may account for the differing results of earlier studies. We conclude that IL-4 promotes the development of a noncytolytic CD8(low) T cell phenotype that might be important in tumor- or pathogen-induced immune deviation.

Increase in prevalence of nosocomial non-Candida albicans candidaemia and the association of Candida krusei with fluconazole use

Candida is an important nosocomial pathogen. This study was undertaken to provide information on the rate of candidaemia, to define the risks for candidaemia and to describe and account for the epidemiology of candidaemia at our institution between 1992 and 1999. The overall rate was 0.052 per 1000 patient days and 0.27 per 1000 discharges. The major risks for candidaemia were colonization at a non-sterile site (OR 3.85, 95%CI 1.80-9.09), total parenteral nutrition (TPN) in the absence of neutropenia (OR 11.8, 95%CI 4.5-35.4, P

Nitrate ammonification and its relationship to the accumulation of ammonium in a Vertisol subsoil

High concentrations of ammonium ( up to 270 kg N/ha) have been observed in a Vertisol soil below 1 m depth near Warra in south-east Queensland. This study examined the possibility that increased water movement into the subsoil after the removal of native vegetation, and a subsequent increase in periods of waterlogging, could have triggered nitrate ammonification and be responsible for the production of ammonium. Two incubation experiments were conducted to test this hypothesis. The first involved the incubation of repacked cores that had been amended with 30 mg N/kg of 5 atom% N-15 nitrate under low oxygen conditions for a period of 360 days. Over this time period the N-15 enrichment of the exchangeable ammonium fraction was monitored in order to detect any reduction of nitrate to ammonium. The second experiment involved the incubation of soil amended with 30 mg N/ kg of 5 atom% N-15 nitrate under waterlogged and low oxygen conditions for 75 days. During this period the redox potential of the soil was monitored using a field test to determine if reducing conditions would develop in this soil over a period of waterlogging, combined with the monitoring of any nitrate reduction to ammonium. The results of these experiments indicated that a small amount of nitrate ammonification (< 0.1 mg N/ kg) could be observed in the Warra subsoil, but that unless the rate of reduction were to significantly increase with time, this could not account for the accumulation of ammonium observed in the field. The environmental conditions that would make either dissimilatory or abiotic nitrate ammonification favourable were not observed to develop. Consequently, it has been concluded that the observed nitrate ammonification occurred via an assimilatory pathway. Due to the low rate of microbial activity in this subsoil it is considered unlikely that this process was responsible for the subsoil ammonium accumulation at Warra.