A palaeopathological analysis of skeletal remains from Bronze Age Mongolia.

Little is known about the lifeways of the people who inhabited the Mongolian steppe during the Bronze Age (c. 4450-2650 BP). Palaeopathological analysis allows us to draw inferences about the lifeways of past people from the indicators of health and lifestyle recorded in human remains. This paper presents results of analysis of the remains of 25 individuals excavated in northern Mongolia. Overall, the remains demonstrated very little pathology. In particular the lack of evidence for both infectious and non-communicable diseases, along with the patterns of dental pathology indicate a group of people who experienced few health insults and little stress. The types of trauma, Schmorl's nodes and patterns of degenerative joint disease present in the sample are suggestive of interpersonal violence and horse riding. The findings are consistent with a traditional pastoral lifeway where people live in small groups, rely on a protein-rich diet and use animals for transportation.

Characterization of interleukin 2-dependent cytotoxic T-cell clones. IV. Production of alpha, beta and gamma interferons and interleukin 2 by Lyt-2+ T cells.

The production of alpha, beta and gamma interferons (IFN) and interleukin 2 (IL-2) by Lyt-2+-dependent cytotoxic T-cell lines/clones was investigated. Cloned and uncloned T-cell lines specific for H-2Dd or the unique RL male 1 leukemia antigen were studied. After infection with Sendai virus (SV) or Newcastle disease virus (NDV) all cell lines produced IFN-alpha and -beta. Induction of IFN-gamma was attempted with the mitogens Con A, PHA, PWM, SEA, and SEB, with poly(I:C), with antibodies Lyt-1.2, -2.2, and Thy-1.2, or with the target cells Meth A (H-2Dd+) and RL male 1. All mitogens were effective inducers. However, the antibodies and poly(I:C) were not. One uncloned RL male 1-specific cell line CTLL-RP, produced IFN-gamma after induction with RL male 1. Production of IFN-alpha, beta depended on IL-2, whereas production of IFN-gamma did not, although addition of highly purified IL-2 increased IFN-gamma production even in the absence of other inducers. Crude IL-2 inhibited the production of IFN-gamma but not IFN-alpha, beta. In response to mitogens, some T-cell clones also produced IL-2. The results demonstrate that Lyt-2+ cells can produce a broad spectrum of lymphokine activities after appropriate stimulation. Their availability now affords us the opportunity to study the regulation of lymphokine production at the clonal level.

Multiple lymphokine production by a phorbol ester-stimulated mouse thymoma: relationship to cell cycle events.

Interleukin 2 (IL-2) production was studied in a subclone of the murine thymoma EL 4. Phenotypic characterization revealed the EL 4-17-2 line to be Thy-1.2+, Lyt-1.2+, and Lyt-2.2-. Costimulation with 500 ng 12-O-tetradecanoylphorbol 13-acetate (TPA)/ml and 5 micrograms concanavalin A (Con A)/ml induced optimal levels of IL-2. Three related phorbol esters stimulated comparable levels of IL-2 when used in conjunction with Con A. Kinetic experiments indicated that IL-2 first became detectable at 2 hours in TPA-treated cultures, whereas in cultures stimulated with Con A alone IL-2 production was not evident until 8 hours. Flow cytometry indicated that TPA and its related phorbol esters cause a perturbation in the cycling of the cell which may be related to increased IL-2 production. Under the conditions examined, no interferon-gamma (IFN-gamma) was detectable. Conversely, both granulocyte-macrophage colony-stimulating factor (CSF-GM) and interleukin-3 (IL-3) were found under conditions that led to stimulation of IL-2 synthesis. CSF-GM was produced in cultures treated singly with 500 ng TPA/ml or with Con A. IL-3 production was similar to IL-2 production, because optimal levels were found in cultures after combined treatment with phorbol ester and mitogen.

Purified human interleukin-2 enhances induction of immune interferon.

Interleukin-2 (IL-2), purified to apparent homogeneity, enhanced interferon (IFN) production in phytohemagglutin (PHA)-stimulated cultures of Ficoll-Hypaque-purified human mononuclear cells derived from plateletpheresis residues. Cells incubated with IL-2 in the absence of PHA did not produce detectable IFN. Neutralization with specific antisera and lack of activity in bovine cells indicated that the IFN produced in cells treated with IL-2 was IFN gamma. Addition of IL-2 to cultures stimulated IFN production in a dose-dependent fashion, with 100 U/ml of IL-2 generally producing optimal stimulation. There was considerable variability in the magnitude of the IFN response and the degree of its enhancement by IL-2 treatment in cells from different donors. However, an enhancement of IFN production after treatment with 100 U/ml of IL-2 was regularly observed in 11 experiments, with the increase ranging from 3- to 37-fold (mean 8.6-fold). The difference between IFN yields in control cultures and cultures treated with 100 U/ml of IL-2 was statistically significant (P less than 0.001). In contrast, 1000 U/ml of IL-2 strongly inhibited IFN induction by PHA. Treatment of cultures with IL-2 did not alter the kinetics of IFN production which peaked at 48-72 hr after PHA stimulation. When PHA was added only 24 to 96 hr after the establishment of cultures, rather than at the time of their seeding, both IFN production and endogenous IL-2 production were enhanced. The addition of exogenous IL-2 to such cultures caused only a modest further enhancement of IFN production. These data suggest that a threshold concentration of IL-2 (exogenously added or endogenously produced) is required for optimal IFN gamma production by human mononuclear cells.

Stimulation of lymphokine production by teleocidin, aplysiatoxin, and debromoaplysiatoxin.

Previous studies showed that the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) and several structurally related tumor-promoting compounds stimulate lymphocytes to produce immune interferon (IFN-gamma) and interleukin 2 (IL-2). This study shows that three compounds structurally unrelated to TPA, previously shown to mimic TPA in some other biological activities, are similar to TPA in stimulating IFN-gamma and Il-2 production in cultures of human peripheral blood lymphocytes. The production of another lymphokine, termed lymphotoxin (LT), was also enhanced by TPA and the other three compounds examined. Maximal enhancement of lymphokine production was observed in cultures costimulated with TPA or one of the other tested compounds and phytohemagglutinin (PHA). TPA was separated from IFN-gamma during a multistep purification procedure.

Coproduction of interleukin-2 and interferon-gamma in human mononuclear cells.

Interleukin-2 (IL-2) and immune interferon (IFN-gamma) production was studied in Ficoll-hypaque purified human mononuclear cells derived from plateletpheresis residues. As previously reported, costimulation by 5 ng/ml of 12-O-tetradecanoylphorbol-13-acetate (TPA) and 5 microgram/ml of phytohemagglutinin (PHA) caused a marked enhancement of IFN-gamma levels compared to the yields obtained with PHA alone. IL-2 levels were also increased 50-300 times by this induction protocol. Mezerein (MZN), a compound structurally related to TPA, was found to be similar to TPA in enhancing IFN-gamma and IL-2 levels. In addition to TPA and MZN, four other related phorbol esters caused a stimulation of IFN-gamma and IL-2, with the production of IL-2 paralleling the production of IFN-gamma. Kinetic experiments indicate that low levels of IL-2 first became detectable 6 h after induction, whereas IFN-gamma could be demonstrated only later. Furthermore, IL-2 production reached a plateau earlier than IFN-gamma production in the TPA/PHA treated cultures. Dialysis at pH 2 abrogated the IFN-gamma activity but not the IL-2 activity. A three-step purification procedure developed for IFN-gamma isolation effectively separated IFN-gamma from IL-2. Our results show that there is a close correlation between the magnitude of IL-2 and IFN-gamma production under the experimental conditions employed. Physical separation of the two lymphokines is important for future studies on the interactions between IFN-gamma and IL-2 in various cellular immune reactions.