One of the factors that may influence the cytokine secretion profile of a T cell is the antigen-presenting cell (APC). Since activated human T cells have been described to express major histocompatibility complex (MHC) class II molecules as well as costimulatory molecules for T cell activation, like e.g. ICAM-1, LFA-3 and B7, they might play a role as APC and be involved in the regulation of T-Tcell interactions. To define further the role of T cells as APC we tested their capacity to induce proliferation and cytokine production in peptide- or allospecific T cell clones and compared it with conventional APC, like B lymphoblasts (B-LCL) or HTLV-1-transformed T cells, or with non-classical APC, like activated keratinocytes or eosinophils. CD4+, DP-restricted T cell clones specific for a tetanus toxin peptide (amino acids 947-967) and CD4+, DR-restricted allospecific T cell clones produced interleukin (IL)-2, IL-4, tumor necrosis factor-alpha and interferon-gamma (IFN-gamma) after phorbol 12-myristate 13-acetate and ionomycin stimulation and a more restricted cytokine pattern after antigen stimulation. Dose-response curves revealed that the antigen-presenting capacity of activated, MHC class II+, B7+ T cells was comparable to the one of B-LCL. Both APC induced the same cytokine profile in the T cell clones despite a weaker proliferative response with T cells as APC. Suboptimal stimulations resulted in a lower IFN-gamma/IL-4 ratio. Cytokine-treated, MHC class II+ keratinocytes and eosinophils differed in the expression of adhesion molecules and their capacity to restimulate T cell clones. The strongly ICAM-1-positive keratinocytes induced rather high cytokine levels. In contrast, eosinophils, which express only low densities of MHC class II and no or only low levels of adhesion molecules (B7, ICAM-1 and LFA3), provided a reduced signal resulting in a diminished IFN-gamma/IL-4 ratio. We conclude that non-classical APC differ in their capacity to restimulate T cell clones, whereby the intensity of MHC class II and adhesion molecules (B7, ICAM-1) expressed seems to determine the efficacy of this presentation.

The natural killer (NK) cell activity of mice in the peritoneal cavity is very low or undetectable and testing peritoneal NK cells is a useful model for studying the influence of activating substances upon local injection. Injection of tumor necrosis factor (TNF) at doses of 10-200 ng caused a marked activation of NK cell activity which was maximal after 24 h and declined rapidly on day 2. A similar effect was observed when interferons alpha and beta were injected, and there were additive results when interferon was injected together with TNF. The NK cell nature of the effector cells activated by TNF was substantiated by the finding that previous injection with anti-asialo GM 1 antibody prevented activation. Interferon could not be detected in the peritoneal wash fluid after injection of TNF suggesting interferon-independent activation. In further experiments after i.p. injection of TNF peritoneal exudate cells (PECs) only killed YAC-1 targets in a 4-h assay. There was no additional killing in an 18-h assay towards neither YAC-1 cells or P815 cells, suggesting that macrophages were not involved. Furthermore TNF was also active in vitro by activating NK cells in isolated human peripheral blood cells. However in the PECs stimulated in vitro no significant induction of cytotoxic capacities by TNF was measured. Our data suggest that the action of TNF is not restricted to the lysis of tumor cells but can also induce immunological properties in the host defense against virus infections and neoplasms.

One of the leading causes of preterm labour is a subclinical intrauterine infection. The diagnosis of this inapparent infection is an unsolved problem, because clinical parameters show the infection mostly too late and cannot be used for early detection of women at high risk for preterm labour. A prospective clinical study measuring cytokines and cytokine receptor concentration in amniotic fluid from patients with preterm labour and preterm rupture of membranes (PROM) was undertaken to answer the question whether the amount of cytokines is positively correlated to the risk of preterm delivery. In 78 patients (43 controls, 23 patients with PROM, 7 with preterm labour and delivery < 37 weeks of gestation, 7 with preterm labour and delivery at term) amniotic fluid was collected and the following cytokines were measured by an ELISA: IL1 beta, IL2, IL6, TNF alpha, IFN gamma, TNF receptor 55 und 75, IFN gamma receptor, IL2 receptor. We found significant, in some cases highly significant differences in the cytokine content of amniotic fluid of patients with PROM compared with controls and patients with preterm labour and delivery before 37 weeks of gestation compared with controls. There were no differences between patients with preterm labour and delivery at term and controls. Amniotic fluid cultures were positive only in 20-25% of the cases and therefore not a predictive sign. The determination of cytokines in amniotic fluid of patients with preterm labour seems to be a good marker to predict the risk of preterm delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

Comparing OKT3 and antithymocyte globulin (ATG) in a prospective study, the dosage difference in regard to body weight (ATG: dependent on body weight/OKT3: independent) does not introduce any obvious source of mistake concerning clinical effectiveness or side effects. One explanation for the lack of influence of body weight may be the high effectiveness of 5 mg of 0KT3, reaching a maximal effect even with lower plasma levels in heavier patients. We wonder, therefore, whether the OKT3 dosage could be lowered.