Cells expressing indoleamine 2,3-dioxygenase inhibit T cell responses

Pharmacological inhibition of indoleamine 2,3-dioxygenase (IDO) activity during murine gestation results in fetal allograft rejection and blocks the ability of murine CD8(+) dendritic cells to suppress delayed-type hypersensitivity responses to tumor-associated peptide Ags. These observations suggest that cells expressing IDO inhibit T cell responses in vivo. To directly evaluate the hypothesis that cells expressing IDO inhibit T cell responses, we prepared IDO-transfected cell lines and transgenic mice overexpressing IDO and assessed allogeneic T cell responses in vitro and in vivo. T cells cocultured with IDO-transfected cells did not proliferate but expressed activation markers. The potency of allogeneic T cell responses was reduced significantly when mice were preimmunized with IDO-transfected cells. In addition, adoptive transfer of alloreactive donor T cells yielded reduced numbers of donor T cells when injected into IDO-transgenic recipient mice. These outcomes suggest that genetically enhanced IDO activity inhibited T cell proliferation in vitro and in vivo. Genetic manipulation of IDO activity may be of therapeutic utility in suppressing undesirable T cell responses.     

Thermoregulation by kangaroos from mesic and arid habitats: influence of temperature on routes of heat loss in eastern grey kangaroos (Macropus giganteus) and red kangaroos (Macropus rufus)

We examined thermoregulation in red kangaroos (Macropus rufus) from deserts and in eastern grey kangaroos (Macropus giganteus) from mesic forests/woodlands. Desert kangaroos have complex evaporative heat loss mechanisms, but the relative importance of these mechanisms is unclear. Little is known of the abilities of grey kangaroos. Our detailed study of these kangaroos' thermoregulatory responses at air temperatures (T(a)) from -5 degrees to 45 degrees C showed that, while some differences occur, their abilities are fundamentally similar. Both species show the basic marsupial characteristics of relatively low basal metabolism and body temperature (T(b)). Within the thermoneutral zone, T(b) was 36.3 degrees + or - 0.1 degrees C (X + or - SE) in both species, and except for a small rise at T(a) 45 degrees C, T(b) was stable over a wide range of T(a). Metabolic heat production was 25% higher in red kangaroos at T(a) -5 degrees C. At the highest T(a) (45 degrees C), both species relied on evaporative heat loss (EHL) to maintain T(b); both panting and licking were used. The eastern grey kangaroo utilised panting (76% of EHL) as the principal mode of EHL, and while this was so for red kangaroos, cutaneous evaporative heat loss (CEHL) was significant (40% of EHL). CEHL appeared to be mainly licking, as evidenced from surface temperatures. Both species utilised peripheral vascular adjustments to control heat flow, as indicated by changes in dry conductance (C(dry)). At lower temperatures, C(dry) was minimal, but it increased significantly at T(a) just below T(b) (33 degrees C); in these conditions, the C(dry) of red kangaroos was significantly higher than that of eastern grey kangaroos, indicating a greater reliance on dry heat loss. Under conditions where heat flows into the body from the environment (T(a) 45 degrees C), there was peripheral vasoconstriction to reduce this inflow; C(dry) decreased significantly from the values seen at 33 degrees C in both kangaroos. The results indicated that, while both species have excellent thermoregulatory abilities, the desert red kangaroos may cope better with more extreme temperatures, given that they respond to T(a) 45 degrees C with lower respiratory evaporation than do the eastern grey kangaroos.     

Changes in carotenoids, tocopherols and diterpenes during drought and recovery, and the biological significance of chlorophyll loss in Rosmarinus officinalis plants

Two-year-old rosemary (Rosmarinus officinalis L.) plants were subjected to severe stress by exposure to prolonged drought during a Mediterranean summer. Severely stressed plants recovered completely after the autumn rainfalls although the relative water content remained below 35% for 3 months and the chlorophyll content of leaves was reduced by up to 85% during the drought. In severe stress: (i) α-tocopherol increased 9-fold per g dry weight and 20-fold per unit of chlorophyll; (ii) lutein and β-carotene contents decreased on a dry-weight basis, but an 80% increase in lutein and constant levels of β-carotene were observed on a chlorophyll basis; (iii) there were transient and sustained increases in the de-epoxidation state of the xanthophyll cycle; and (iv) the highly oxidised abietane diterpene isorosmanol increased 8-fold as a result of the oxidation of carnosic acid. With the autumn rainfalls, water status, α-tocopherol and violaxanthin recovered first and the levels of photosynthetic pigments and abietane diterpenes increased later. The photoprotection conferred by the xanthophyll cycle and the antioxidant function of tocopherols, lutein and diterpenes may help to avoid irreversible damage in severe drought, making possible the recovery of functional membranes after the autumn rainfalls. Besides, chlorophyll loss reduces the amount of photons absorbed by leaves, which enhances the photoprotective and antioxidant capacity of leaves per amount of photons absorbed, since the ratios of xanthophylls, α-tocopherol and abietane diterpenes to chlorophyll increase. Received: 12 July 1999 / Accepted: 25 November 1999     

Induced root-secreted phenolic compounds as a belowground plant defense

Rhizosphere is the complex place of numerous interactions between plant roots, microbes and soil fauna. Whereas plant interactions with aboveground organisms are largely described, unravelling plant belowground interactions remains challenging. Plant root chemical communication can lead to positive interactions with nodulating bacteria, mycorriza or biocontrol agents or to negative interactions with pathogens or root herbivores. A recent study¹ suggested that root exudates contribute to plant pathogen resistance via secretion of antimicrobial compounds. These findings point to the importance of plant root exudates as belowground signalling molecules, particularly in defense responses. In our report,² we showed that under Fusarium attack the barley root system launched secretion of phenolic compounds with antimicrobial activity. The secretion of de novo biosynthesized t-cinnamic acid induced within 2 days illustrates the dynamic of plant defense mechanisms at the root level. We discuss the costs and benefits of induced defense responses in the rhizosphere. We suggest that plant defense through root exudation may be cultivar dependent and higher in wild or less domesticated varieties.Key words: root exudates, plant defense, t-cinnamic acid, fusarium, induced defensePlants grow and live in very complex and changing ecosystems. Because plants lack the mobility to escape from attack by pathogens or herbivores, they have developed constitutive and in addition inducible defenses that are triggered by spatiotemporally dynamic signaling mechanisms. These defenses counteract the aggressor directly via toxins or defense plant structures or indirectly by recruitment of antagonists of aggressors. Whereas induced defenses are well described in aboveground interactions, evidence of the occurrence of such mechanisms in belowground interactions remains limited. The biosynthesis of a defensive molecule could be both constitutive and inducible with a low level of a preformed pool (Fig. 1). In addition, upon encounter of an attacking organism, those levels could be induced to rise locally to a high level of active compound that is able to disarm the pathogen.^2,3 Only a few examples show that root exudates play a role in induced plant defense. Hairy roots of Ocimum basilicum secrete rosmarinic acid only when challenged by the pathogenic fungus Pythium ultimum.⁴ Wurst et al.⁵ reported on the induction of irridoid glycosides in root exudates of Plantago lanceolata in presence of nematodes. In vivo labelling experiments² with ¹³CO₂ showed the induction of phenolic compounds secreted by barley roots after Fusarium graminearum infection and the de novo biosynthesis of root secreted t-cinnamic acid within 2 days. These results show that the pool of induced t-cinnamic acid originated from both pre-formed and newly formed carbon pools (Fig. 1), highlighting a case of belowground induced defense inside and outside the root system.Open in a separate windowFigure 1Suggested mechanisms for the induction of root defense exudates in barley in response to Fusarium attack. Upon pathogen attack by Fusarium, the initial preformed pool of phenolic compounds is increased by the addition of inducible, de novo biosynthesized t-cinnamic acid. Both, the preformed pool and the de novo biosynthesized pool fuel the exudation of defense compounds from infected roots.The concept of fitness costs is frequently presented to explain the coexistence of both constitutive and induced defense.⁶ In the case of induced defense, resources are invested in defenses only when the plant is under attack. In the absence of an infection, plants can optimize allocation of their resources to reproduction and growth to compete with neighbours.⁷ Constitutive defenses are thought to be more beneficial when the probability of attack is high, whereas adjustable, induced defenses are more valuable to fight against an unpredictable pathogen. Non disturbed soil is a heterogeneous matrix where biodiversity is very high and patchy^8,9 and organism motility is rather restricted.¹⁰ As a consequence of the patchiness, belowground environment is expected to be favourable to selection for induced responses.¹¹ The absence of defense root exudates between two infections may form an unpredictable environment for soil pathogens and reduce the chance for adaptation of root attackers. Plants may also use escape strategies to reduce the effect of belowground pathogens. Henkes et al. (unpublished) showed that Fusarium-infected barley plants reduced carbon allocation towards infected roots within a day and increased allocation carbon to uninfected roots. These results illustrate how reallocation of carbon toward non infected root parts represents a way to limit the negative impact of root infection.We have demonstrated the potential of barley plants to defend themselves against soil pathogen by root exudation.² Even the barley cultivar ‘Barke’ used in our study, a modern cultivated variety, was able to launch defense machinery via exudation of antimicrobial compounds when infected by F. graminearum. We suggest that plant defense through root exudation might be cultivar dependent and perhaps higher in wild or less domesticated varieties. Taddei et al.¹² reported that constitutivelyproduced root exudates from a resistant Gladiolus cultivar inhibit spore germination of Fusarium oxysporum whereas root exudates from a susceptible cultivar do not affect F. oxysporum germination. Root exudates from the resistant cultivar contained higher amounts of aromaticphenolic compounds compared to the susceptible cultivar and these compounds may be responsible for the inhibition of spore germination. Metabolic profiling of wheat cultivars, ‘Roblin’ and ‘Sumai3’, respectively, susceptible and resistant to Fusarium Head Blight, showed that t-cinnamic acid was a discriminating factor responsible for resistance/defense function.¹³ Therefore it is likely that wild barley varieties hold higher defense capacities compare to cultivated varieties selected for high yield. In the future, plant breeders in organic and low-input farming could use root-system defense ability as new trait in varietal variation.     

Contralateral effects of unilateral resistance training: a meta-analysis.

It is often claimed that strength training of one limb increases the strength of the contralateral limb, but this has not been demonstrated consistently, particularly in well-controlled studies. The aim was to quantitatively combine the results of other studies on the effects of unilateral training on contralateral strength in humans to provide an answer to this physiological question. We analyzed all randomized controlled studies of voluntary unilateral resistance training that used training intensities of at least 50% of maximal voluntary strength for a minimum of 2 wk. Studies were identified by computerized and hand searches of the literature. Data on changes in strength of contralateral and control limbs were extracted and statistically pooled in a meta-analysis. This approach allows conclusions to be based on a statistically meaningful sample size, which might be difficult to achieve in other ways. Seventeen studies met the inclusion criteria, and 13 provided enough data for statistical pooling. The contralateral effects of strength training reported in individual studies varied from -2.7 to 21.6% of initial strength. The pooled estimate of the effect of unilateral resistance training on the maximal voluntary strength of the contralateral limb was 7.8% (95% confidence interval: 4.1-11.6%). This was 35.1% (95% confidence interval: 20.9-49.3%) of the effect on the trained limb. Pooling of all available data shows that unilateral strength training produces modest increases in contralateral strength.     

Polymorphism in intron 1 of the interferon-gamma gene influences both serum immunoglobulin E levels and the risk for chronic hepatitis B virus infection in Polynesians

Intron 1 of the interferon-gamma (IFNG) gene contains two polymorphisms. The 12 CA-repeat allele of the +875 IFNGCA microsatellite and the T allele of the +A874T single nucleotide polymorphism (SNP) have been associated with increased in vitro IFNG production and a variety of clinical phenotypes. The purpose of this study was to determine whether these polymorphisms influence total serum IgE levels [tsIgE] and the outcome of a hepatitis B virus (HBV) infection. IFNGCA and +A874T were typed in 186 asthmatics of Niuean ancestry and in Polynesian women with a chronic HBV infection (n = 60) and with natural immunity to the HBV (n = 66). The IFNGCA genotype was associated with [tsIgE] in asthmatic children (n = 51, p = 0.004) but not adults (n = 135, p = 0.87). The data were consistent with a co-dominant influence of the 12 CA-repeat allele on high [tsIgE]. The IFNGCA genotype was also associated with the risk for chronic HBV infection (χ ² = 11.6, p = 0.003) because of a dominant effect of the 12 CA-repeat allele on developing natural immunity in homozygotes (OR = 5.8, p = 0.003) and heterozygotes (OR = 2.7, p = 0.01). Similar associations were found for the T allele of the +A874T SNP. The possibility that these associations were due to linked alleles in the adjacent 783 bp of the promoter and 3′-untranslated region of the IFNG gene was excluded by direct sequencing. In summary, high-IFNG-producing alleles in intron 1 of the IFNG locus are associated with high [tsIgE] in asthmatic children from Niue and with natural immunity to the HBV in Polynesian women. These findings are consistent with a previous report of an association between +875 IFNGCA and [tsIgE] and provide preliminary evidence of a new association with the outcome of an HBV infection.