Degassing of early-formed planetesimals restricted water delivery to Earth.

The timing of delivery and the types of body that contributed volatiles to the terrestrial planets remain highly debated1,2. For example, it is unknown if differentiated bodies, such as that responsible for the Moon-forming giant impact, could have delivered substantial volatiles3,4 or if smaller, undifferentiated objects were more probable vehicles of water delivery5-7. Here we show that the water contents of minerals in achondrite meteorites (mantles or crusts of differentiated planetesimals) from both the inner and outer portions of the early Solar System are ≤2 µg g-1 H2O. These are among the lowest values ever reported for extraterrestrial minerals. Our results demonstrate that differentiated planetesimals efficiently degassed before or during melting. This finding implies that substantial amounts of water could only have been delivered to Earth by means of unmelted material.

Dose-dependent effects of dietary gamma-linolenic acid on rat spleen lymphocyte functions.

Feeding rodents a diet rich in evening primrose oil (EPO), which contains 5-10 g gamma-linolenic acid (GLA)/100 g total fatty acids, has been shown to decrease lymphocyte proliferation and natural killer cell activity. However, EPO contains a very high level of linoleic acid which itself can affect lymphocyte functions and it is not clear to what extent the effects of EPO can be attributed to GLA. The current study investigated the effect of two levels of GLA in the rat diet upon immune cell functions; the level of linoleic acid was maintained below 30 g/100 g total fatty acids. Weanling rats were fed on high fat (178 g/kg) diets which contained 4.4 g or 10 g GLA/100 g total fatty acids in place of a proportion of linoleic acid. The total polyunsaturated fatty acid content and the n-6 to n-3 polyunsaturated fatty acid ratio of the diet were maintained at 35 g/100 g total fatty acids and 7, respectively. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet, with an increase in the proportions of GLA and dihomo-gamma-linolenic acid when the diets containing GLA were fed; these diets also increased the proportion of arachidonic acid in spleen leukocytes. Spleen lymphocyte proliferation in response to concanavalin A was significantly reduced (by 60%) by feeding the diet containing the higher level of GLA, but not by the diet containing the lower level of GLA. Spleen natural killer cell activity and prostaglandin E (PGE) production by spleen leukocytes were not significantly affected by inclusion of GLA in the diet, although there was a tendency towards decreased natural killer cell activity by cells from rats fed the high GLA diet. Thus, this study shows that dietary GLA is capable of altering the fatty acid composition of cells of the immune system and of exerting some immunomodulatory effects, but that the level of GLA in the diet must exceed 4.4 g/100 g total fatty acids for these effects to become apparent.

Autoreactive and immunoregulatory T-cell subsets in insulin-dependent diabetes mellitus.

AIMS/HYPOTHESIS: Type I (insulin-dependent) diabetes mellitus is a T-cell mediated autoimmune disease. Several subsets of T-cells, in particular CD4+ and in vivo activate CD45RA+RO+ T-cells, have been shown to be increased at disease onset. The functional implications of these relative increases in CD4 T-cells were investigated. METHODS: Subsets of T-cells were sorted on the basis of their activation status (CD45RA+ naive cells, CD45RA+RO+ recently activated cells and CD45RO+ memory cells) and stimulated with autoantigens or recall antigen in vitro. RESULTS: Proliferative responses to tetanus toxoid were primarily or exclusively observed in resting memory T-cells (CD45RO+). Autoimmune T-cell responses were, however, primarily measured in activated T-cells (CD45RA+RO+) in newly diagnosed Type I diabetic patients, whereas those with longer disease duration reacted to autoantigens with memory T-cells (CD45RO+) (p < 0.004). Interestingly, in non-diabetic control subjects not responding to autoantigens in the regular assay, considerable autoreactive T-cell responses were detectable after sorting in the CD45RO+ or CD45RA+RO+ lymphocyte subsets. Remixing these subsets showed that these autoimmune responses in activated cells could be down-modulated by CD45RA+ lymphocytes, whereas resting memory cells appeared unaffected by the suppressive CD45RA subset. CONCLUSION/INTERPRETATION: These results show that autoimmune T-cell responses can be linked to particular subsets which differ depending on clinical status. Furthermore, the CD45RA T-cell subset harbours lymphocytes potentially capable of suppressing autoimmune T-cell responses. The changes in responsiveness to exogenous insulin may help to unravel the mechanism by which isohormonal therapy could prevent the onset of Type I diabetes.

Manipulation of the type of fat consumed by growing pigs affects plasma and mononuclear cell fatty acid compositions and lymphocyte and phagocyte functions.

To investigate the immunological effect of feeding pigs different dietary lipids, 3-wk-old, weaned pigs were fed for 40 d on one of five diets, which differed only in the type of oil present (the oil contributed 5% by weight of the diet and the total fat content of the diets was 8% by weight). The oils used were soybean (control diet), high-oleic sunflower oil (HOSO), sunflower oil (SO), canola oil (CO), and fish oil (FO; rich in long-chain [n-3] polyunsaturared fatty acids). There were no significant differences in initial or final animal weights, weight gains, or health scores among the groups. There were no significant differences in the concentration of anti-Escherichia coli vaccine antibodies in the gut lumens of pigs fed the different diets. The fatty acid composition of the diet markedly affected the fatty acid composition of the plasma and of mononuclear cells (a mixture of lymphocytes, monocytes, and macrophages) prepared from the blood, lymph nodes, or thymus. The FO feeding resulted in a significant increase in the number of circulating granulocytes. The FO feeding significantly decreased the proportion of phagocytes engaged in uptake of E. coli and decreased the activity of those phagocytes that were active. The proliferation of lymphocytes in cultures of whole blood from pigs fed the HOSO, SO, or FO diets was less than in those from pigs fed the CO diet. Proliferation of lymph node lymphocytes from SO- or FO-fed pigs was less than that from control, CO-, or HOSO-fed pigs. The natural killer cell activity of blood lymphocytes from pigs fed the FO diet was significantly reduced compared with those from pigs fed the CO diet. The concentration of PGE2 in the medium of cultured blood, lymph node, or thymic mononuclear cells was lower if the cells came from pigs fed the FO diet. Thus, the type of oil included in the diet of growing pigs affects the numbers and functional activities of immune cells in different body compartments.

Low levels of eicosapentaenoic and docosahexaenoic acids mimic the effects of fish oil upon rat lymphocytes.

Fish oil is rich in the long chain n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); typically these fatty acids constitute 20 to 25 g/100 g total fatty acids in fish oil. Feeding rodents diets rich in fish oil has been shown to decrease lymphocyte proliferation and natural killer cell activity. It is not known what level of EPA + DHA is required in the diet to exert these effects. This question was addressed in the current study. Weanling rats were fed on high fat (178 g/kg) diets which contained 4.4 g alpha-linolenic acid (control) or 4.4 g EPA + DHA (4.4 EPA + DHA) or 6.6 g EPA + DHA (6.6 EPA + DHA)/100 g total fatty acids. The n-6 to n-3 polyunsaturated fatty acid ratio was maintained at approximately 7. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet. Spleen lymphocyte proliferation in response to concanavalin A, spleen natural killer cell activity and PGE2 production by spleen leukocytes were reduced by feeding the EPA + DHA diets compared with feeding the control diet; the 4.4 and 6.6 EPA + DHA diets caused very similar reductions. The 4.4 EPA + DHA diet reduced popliteal lymph node weight following a localised graft versus host response; this response was not investigated in rats fed the 6.6 EPA + DHA diet. The reductions in lymphocyte functions and in the in vivo graft versus host response caused by the EPA + DHA diets were similar to those previously reported following the feeding of diets rich in fish oil. Thus, this study shows that diets containing relatively low levels of EPA + DHA (20 to 25% of the level found in fish oil) exert immunomodulatory effects. Furthermore, this study suggests that the maximal effect of EPA + DHA is exerted when these fatty acids constitute a level of less than or equal to 4.4 g/100 g total dietary fatty acids.

Eicosapentaenoic and docosahexaenoic acids alter rat spleen leukocyte fatty acid composition and prostaglandin E2 production but have different effects on lymphocyte functions and cell-mediated immunity.

Weanling rats were fed on high-fat (178 g/kg) diets which contained 4.4 g alpha-linolenic (ALA), gamma-linolenic, arachidonic (ARA), eicosapentaenoic (EPA), or docosahexaenoic acid (DHA)/100 g total fatty acids. The proportions of all other fatty acids, apart from linoleic acid, and the proportion of total polyunsaturated fatty acids (PUFA) (approximately 35 g/100 g total fatty acids) were constant, and the n-6 to n-3 PUFA ratio was maintained as close to 7 as possible. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet. Prostaglandin E2 production was enhanced from leukocytes from rats fed the ARA-rich diet and was decreased from leukocytes from the EPA- or DHA-fed rats. Replacing dietary ALA with EPA resulted in diminished ex vivo lymphocyte proliferation and natural killer (NK) cell activity and a reduced cell-mediated immune response in vivo. In contrast, replacing ALA with DHA reduced ex vivo lymphocyte proliferation but did not affect ex vivo NK cell activity or the cell-mediated immune response in vivo. Replacement of a proportion of linoleic acid with either gamma-linolenic acid or ARA did not affect lymphocyte proliferation, NK cell activity, or the cell-mediated immune response. Thus, this study shows that different n-3 PUFA exert different immunomodulatory actions, that EPA exerts more widespread and/or stronger immunomodulatory effects than DHA, that a low level of EPA is sufficient to influence the immune response, and that the immunomodulatory effects of fish oil may be mainly due to EPA.