Herpesvirus saimiri is a primate tumor virus and induces acute T cell lymphomas and leukemias in New World monkeys and rabbits. We show in this report that infection of human peripheral white blood cells with a group C strain 484-77 results in selective expansion of CD8 lymphocytes with strong cytotoxic activity and these cells do not require interleukin-2 (IL-2) for growth. Infected cell cultures, termed herpesvirus-activated killer (HAK) cells, have been continuously maintained for several months in tissue culture and these HAK cells contain multiple copies of stable circular viral episomes. The growth and cytotoxicity of HAK cells was found independent of IL-2. Analysis of deletion mutant infected cells suggests that at least two open reading frame sequences of a bicistronic mRNA encoded by the viral genome is involved in controlling IL-2 independence. This model could facilitate studies on growth regulation of human cytotoxic T cells that are important effector cells in immune responses against infectious diseases and cancer and should help us to elucidate the mechanism of transformation by H. saimiri oncogenes.

Mannoprotein fractions of Candida albicans were assayed for their effects on the anticandidal activity of human polymorphonuclear leukocytes (PMNL). One fraction, MP-F2, enhanced PMNL inhibition of candidal growth in vitro as potently as bacterial lipopolysaccharide (LPS), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-8. MP-F2-mediated PMNL activation was manifested on yeast and mycelial forms of the fungus, required the integrity of the mannan, and was due to an increase in the actual number of phagocytic PMNL rather than to a greater ingestion of fungal cells by each individual neutrophil. While not inducing augmented O2 production or degranulation of azurophilic granules, MP-F2 strongly stimulated the release of lactoferrin. Lactoferrin inhibited candidal growth in the absence of PMNL, and anti-lactoferrin antibodies reversed both this inhibition and the PMNL activation by MP-F2, GM-CSF, and LPS. Thus, PMNL may be activated by relevant candidal mannoproteins, and release of lactoferrin may add to other antimicrobial mechanisms of PMNL for the control of candidal infections.

Lipopolysaccharides (LPSs) from Escherichia coli, Serratia marcescens, and Salmonella typhimurium, at doses from 1 to 100 ng/ml, strongly enhanced growth inhibition of Candida albicans by human polymorphonuclear leukocytes (PMN) in vitro. Flow cytometry analysis demonstrated that LPS markedly augmented phagocytosis of Candida cells by increasing the number of yeasts ingested per neutrophil as well as the number of neutrophils capable of ingesting fungal cells. LPS activation caused augmented release of lactoferrin, an iron-binding protein which itself could inhibit the growth of C. albicans in vitro. Antibodies against lactoferrin effectively and specifically reduced the anti-C. albicans activity of both LPS-stimulated and unstimulated PMN. Northern (RNA blot) analysis showed enhanced production of mRNAs for interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 and in neutrophils within 1 h of stimulation with LPS. The cytokines were also detected in the supernatant of the activated PMN, and their synthesis was prevented by pretreatment of LPS-stimulated PMN with protein synthesis inhibitors, such as emetine and cycloheximide. These inhibitors, however, did not block either lactoferrin release or the anti-Candida activity of LPS-stimulated PMN. These results demonstrate the ability of various bacterial LPSs to augment neutrophil function against C. albicans and suggest that the release of a candidastatic, iron-binding protein, lactoferrin, may contribute to the antifungal effect of PMN. Moreover, the ability to produce cytokines upon stimulation by ubiquitous microbial products such as the endotoxins points to an extraphagocytic, immunomodulatory role of PMN during infection.

We have previously reported that IL-2-induced lymphokine-activated killer (LAK) cells have the capacity to lyse autologous and allogeneic monocytes. To understand the biologic significance of this interaction, we investigated the function of human monocytes against the opportunistic pathogen, Candida albicans, subsequent to a short exposure to autologous LAK cells. A highly sensitive radiolabel assay, which makes use of the incorporation of [3H]glucose into residual Candida after their incubation with monocytes, was developed to measure antifungal activity. Cultured monocytes, after 2 to 6 h exposure to LAK cells, were found to be substantially suppressed in their ability to control fungal growth. Moreover, monocytes cultured in the presence of granulocyte/macrophage (GM)-CSF or IL-3, were even more suppressed in function after a short incubation with LAK cells. The effect of GM-CSF was both time and dose dependent, with peak susceptibility induced after 4 days of culture with as little as 10 U/ml of the cytokine. These GM-CSF-cultured monocytes, however, were relatively resistant to inhibition by freshly isolated large granular lymphocytic NK cells. Therefore, IL-2 induces in large granular lymphocytic cells the capacity to inhibit monocyte function. In contrast to GM-CSF and IL-3, IFN-gamma was found to have a protective effect on monocytes, because monocytes cultured 4 days in IFN-gamma were not significantly inhibited by LAK cells. These results indicate that LAK cells may be involved in regulation of monocyte function and suggest that the state of differentiation induced by different cytokines may dictate the level of control of the monocytes by LAK cells.

An aerobiologic survey using a rotoslide sampler was conducted daily (January 1979 through December 1981) in Tampa, Florida.A major tree pollen season (Dec. through May) consisted of oak, pine, Australian pine, bald cypress, cedar, bayberry and mulberry. A minor tree season (Oct. and Nov.) consisted of Australian pine and elm. Grass pollen was found throughout the year and most prevalent April through October. A major weed pollen season (May through Dec.) consisted of ragweed, Mexican tea, pigweed, dog fennel, and false nettle. A minor weed season (March through July) consisted of sorrel and dock.

Evidence is presented that human polymorphonuclear neutrophils (PMN) can be induced to produce tumor necrosis factor (TNF). Other investigators have previously reported that TNF has been induced from macrophages by bacteria and, more recently, from natural killer cells by certain tumor cells. Our laboratory has reported that the opportunistic fungi, Candida albicans, can induce TNF, not only from human monocytes, but also from Percoll-fractionated large granular lymphocytes. We now report that incubation of PMN with C albicans for 3 hours was sufficient for detection of TNF release, and peak induction was observed at 8 to 18 hours. This release was inhibitable by actinomycin D, an inhibitor of RNA synthesis, as well as by emetine and cycloheximide, which block protein synthesis. The TNF produced by PMN was neutralized by specific monoclonal antibodies against human TNF. These results represent an important finding that TNF production is a normal response of PMN to stimulation by fungi such as C albicans and suggest that the release of TNF may be related to autocrine activation of PMN effector function to control Candida growth.

Sixty-seven nasal and bronchial provocation tests were performed with Australian pine pollen extract (APE) on 61 subjects. A positive nasal response was elicited in 10 of 14 (71%) subjects with allergic rhinitis and positive APE skin tests and in none of 23 control subjects with negative APE skin tests. A positive bronchial challenge was elicited in 5 of 10 (50%) extrinsic asthmatics with positive APE skin tests and in none of 20 control subjects with negative APE skin tests. Australian pine pollen-specific IgE was demonstrated by conventional RAST (greater than or equal to + 1) in 6 of 14 (42%) subjects with a positive nasal challenge, and in 4 of 5 (80%) subjects with a positive bronchial challenge. The Australian pine pollen is an aeroallergen.

Astemizole is a new H1 histamine-receptor antagonist that has a long elimination half-life and high H1-receptor affinity. This double-blind study evaluated the safety and efficacy of astemizole in the treatment of chronic idiopathic urticaria (more than or equal to 3 months). Seventeen male and 34 female adult patients with chronic idiopathic urticaria entered the 2-month study. After a 48- to 72-hour washout, half the subjects were prerandomized to receive astemizole (10 mg), and the other half received placebo. Placebo-treated patients who were unable to complete the full 8 weeks because of uncontrolled chronic urticaria symptoms were entered into a 2-month open astemizole trial. Treatment with astemizole, as measured at the end point of each patient's treatment and compared to placebo, resulted in significant improvement of pruritus, erythema, number of wheals, frequency of urticarial attacks, and control of urticaria (p ⩽ 0.03). The overall response to astemizole was significantly better than for placebo, according to both the investigator's and the patient's global evaluations (p < 0.01) and as indicated by dropouts caused by treatment failure with placebo (p = 0.005). Six of 26 (24%) of the placebo-treated patients in the double-blind study had good to excellent results on the basis of global assessments. Thirteen of 16 patients with placebo-treatment failures who received astemizole in the open trial improved significantly from baseline symptoms of pruritus, erythema, and number of wheals (p ⩽ 0.05). No significant side effects were reported except mild sedation in three astemizole-treated subjects. Astemizole, a new, potent, long-acting H1 antihistamine, is a safe, effective, and convenient treatment for chronic idiopathic urticaria.

Fifty-seven nasal and bronchial provocation tests were performed with bald cypress pollen extract (BCE) on 41 subjects. A positive nasal response was elicited in 12 of 17 (71%) subjects with allergic rhinitis and positive BCE skin tests, and in none of 16 control subjects. A positive bronchial challenge was elicited in two of ten extrinsic asthmatics with positive BCE skin tests, and in none of 14 control subjects. BCE-specific IgE was demonstrated by RAST in seven of the 12 (59%) subjects with a positive nasal challenge and in one of the two with a positive bronchial challenge. BC pollen is an aeroallergen.