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PubMed2003

Climate, body condition and spleen size in birds.

Climatic conditions may impact on the body condition of animals and thereby affect their survival prospects. However, climate may also impact directly on the survival prospects of animals by affecting the size of immune defence organs that are used for defence against parasites. We used a large long-term database on body condition and size of the spleen in birds to test for immediate and delayed relationships between climatic conditions as indexed by the North Atlantic Oscillation (NAO) and body condition and spleen mass, respectively. Across 14 species of birds, spleen mass was significantly positively correlated with the NAO index, while the delayed effect of NAO on spleen mass was not significant. Spleen mass was positively related to body condition, but body condition did not depend significantly on NAO or delayed NAO effects. Bird species with a strong positive effect of NAO on spleen mass tended to have small spleens for their body size, while species with a strong negative effect of NAO on spleen mass tended to have relatively large spleens. Since bird species with relatively large spleen have been shown to suffer more from the negative effects of parasites, we can infer that the effects of climate as indexed by NAO on the size of the spleen depends on the importance of parasite-mediated natural selection.

Adaptation, Physiological↗
PubMed1991

Large liposomes containing ganglioside GM1 accumulate effectively in spleen.

Large liposomes, with a composition of egg phosphatidylcholine, cholesterol and ganglioside GM1, prepared by an extrusion method, were injected intravenously into mice. After 24 h, up to 50% of injected dose was accumulated in spleen compared with about 15% in spleen for liposomes containing no GM1. The effect of GM1 on spleen accumulation of liposomes was liposome size dependent. Only relatively large liposomes (d greater than 300 nm) showed high accumulation; smaller liposomes were progressively less accumulated. The spleen accumulation increased with increasing injection dose of the liposomes. It was noted that the enhanced uptake by spleen was accompanied by a decrease in the liver uptake, but the total uptake of liposomes by liver and spleen was not dependent on the diameter of liposome or the presence of the ganglioside GM1. Autoradiographs of fixed and sectioned spleen using 125I-labeled tyraminylinulin as a content marker for the liposomes, showed that liposomes localized at the reticular meshwork of the red pulp. These results suggest that larger liposomes containing GM1 are filtered by the spleen during the circulation in blood. The smaller ones with a mean diameter of less than 100 nm are not retained by the filter. The function of GM1 is to prevent liposomes from a rapid uptake by the liver so that liposomes may circulate through the spleen and be filtered. These results, together with the observation that the liposome-entrapped proteins were degraded by the spleen, suggest the potential use of these liposomes for specific drug delivery to the spleen.

Animals↗
PubMed1989

Antigen presentation by neonatal murine spleen cells.

The ability of murine neonatal spleen cells to present soluble antigen to T-helper cells and to produce growth factors in response to subsequent cellular interactions was studied. The T-helper-cell line (D10-G4.1) (D10), which is specific for the soluble antigen conalbumin presented on H-2-matched (H-2k) antigen-presenting cells, was used as cooperating and indicator cells in these cellular interactions. The D10 cells are TH2 T-helper cells which secrete the autocrine growth factor IL-4 and can also respond to exogenous IL-2 (T. R. Mosmann and R. L. Coffmann, Immunol. Today 8, 223, 1987). D10 cells require exogenous IL-1 for their proliferation and secrete, in addition to IL-4, IL-1 inducer factor and GM-CSF. The ability of neonatal spleen cells to present antigen and to stimulate D10 cells to produce IL-4 and proliferate is low. During antigen presentation there is an augmentation of IL-1 and IL-2 production by the antigen-presenting spleen cell population. However, neonatal spleen cells do not respond to the same levels as do adult spleen cells. The addition of exogenous IL-1 cannot repair the antigen presentation by neonatal cells. Experiments in which the antigen processing and presentation steps were separated from those requiring growth factor induction and secretion demonstrate that neonatal spleen cells are impaired in their ability to perform adequate antigen processing and presentation. The neonatal spleen cells are as competent as adult cells to cooperate with T-helper cells and secrete growth factors, provided antigen processing and presentation is performed by fully competent adult spleen cells. Experiments in which neonatal and adult antigen-presenting spleen cell populations were mixed, and others in which plastic adherent and nonadherent cells were separated, could not detect any suppressor mechanisms responsible for the low antigen presentation of neonatal cells. Thus, neonatal spleen cells are impaired in the initial stages of antigen processing and presentation. This impairment which leads to low levels of growth factor production is the major determinant in the ineffectual stimulation of T-helper cells by neonatal spleen cells.

Animals↗
PubMed1994

The role of CD4+ and CD8+ cells in normal F1 hybrid host in the resistance to lethal graft-versus-host disease induction by transfer of parent spleen cells.

Transfer of a certain number of C57BL/6 (B6) spleen cells into (BALB/cxB6)F1 (CB6F1) nu/nu mice, which are deficient in T cells, causes lethal graft-versus-host disease (GVHD) in the recipients. However, when normal CB6F1 mice are used as recipients, lethal GVHD does not occur. Using this lethal GVHD system, we investigated which roles CD4+ and CD8+ T cells play in the resistance to lethal GVHD induction by parent cell transfer in the normal F1 hybrid host. Lethal GVHD induction by B6 spleen cells in CB6F1 nu/nu mice was blocked by prior reconstitution of the recipients with normal syngeneic spleen cells. In addition, all nu/nu mice reconstituted with syngeneic CD8+ spleen cells developed lethal GVHD, whereas none of the nu/nu mice reconstituted with CD4+ cells did. Both spleen weight and number of spleen cells in the former prominently decreased in contrast to the slight increase (peak at 15 weeks) seen in the latter after transfer of donor spleen cells. H-2Dd- Thy1.2+ cells, which are considered to derive from donor B6 T cells, existed in the spleen from the CD4+ spleen cell-reconstituted GVHD mice, peaking at 5 weeks then gradually decreasing after transfer of donor cells. However, they disappeared in the normal spleen cell-reconstituted GVHD mice 5 weeks later. These findings suggest that CD4+ cells in the normal F1 hybrid host play a critical role in the resistance to lethal GVHD induction by parent spleen cell transfer, although CD8+ cells are required for the prompt elimination of donor cells.

Animals↗
PubMed1982

Restoration of impaired immune functions in aging animals. VI. Differential potentiating effect of 2-mercaptoethanol on young and old murine spleen cells.

The differential effect of 2-mercaptoethanol (2-ME) on spleen and bone marrow cells of young and old mice was determined in vitro. Both the ability of spleen cells to proliferate and to generate Ig-secreting cells and the capacity of bone marrow cells to generate myeloid colonies were assessed. All three activities assessed in both young and old mice were enhanced by the presence of 2-ME, but a differential effect with respect to age was noted in only one. This was the polyclonal activating antibody response to bacterial lipopolysaccharide (LPS) in which 2-ME enhanced young spleen cells to a greater extent than old spleen cells, although their mitogenic responses to LPS were enhanced to the same extent. The ability of 2-ME to enhance old spleen B cells to proliferate but not differentiate in their response to LPS would suggest that aging alters certain subpopulations of spleen cells, some of which are sensitive and others insensitive to the potentiation effects of 2-ME. The enhancing action of 2-ME on the proliferative activity of LPS-stimulated young spleen cells was reduced drastically by decreasing the number of T cells by prior treatment of spleen cells with anti-T cell reagent. The proliferative activity was then brought back to normal pretreatment level by adding enriched T cells. Therefore it would appear that regulatory T cells are the target of the enhancing action of 2-ME. The failure of old spleen cells to respond vigorously to the polyclonal activating action of LPS and 2-ME individually and in combination would indicate that age-related alterations may be taking place in the B cells and/or the regulatory cells. Young-old spleen cell mixture study indicates that there are regulatory cells in old spleen cells which can inhibit B cell differentiation but not B cell proliferation.

Adjuvants, Immunologic↗
PubMed1996

Assessment of the contribution of the spleen to granulocytopoiesis and erythropoiesis of the mid-gestation human fetus.

Several current textbooks of hematology describe the spleen of the mid-gestation human fetus as a granulocytopoietic and an erythropoietic organ. Although studies in fetal rodents support this view, a convincing demonstration of such in normal human fetuses is lacking. We tested the hypothesis that the human mid-gestation fetal spleen is normally (1) a site of active granulocytopoiesis and erythropoiesis, or (2) a site of production of specific granulocytopoietic or erythropoietic growth factors. This was accomplished using the spleens, livers, and long-bones of 18 human fetuses, 13-22 weeks gestation, immediately following elective, induced, pregnancy terminations. Organs of some of the abortuses were placed directly into formalin for histologic evaluation. Organs from others were subjected to RNA extraction for subsequent probing for specific hematopoietic growth factor mRNA. Cell suspensions were created from the organs of other abortuses for quantification of the absolute number of neutrophils and erythrocytes and their precursors and progenitors. Evidence of active hematopoiesis was present in marrow and liver but not spleen. Transcripts for granulocyte colony-stimulating factor (G-CSF) were detected in the marrow but not the spleen or liver, and transcripts for erythropoietin (Epo) were detected in the liver but not the spleen or marrow. The populations of hematopoietic progenitor cells and normoblasts in the fetal spleen cell were similar to those in fetal blood. Thus, it is likely that the hematopoietic progenitors recovered from fetal spleen cell suspensions are the result of blood within the spleen, rather than from hematopoiesis within the organ. The spleen of mid-gestation human fetuses, unlike the spleen of fetal rats, does not normally function as an active site of granulocytopoiesis or erythropoiesis, nor is it an active site for production of G-CSF or Epo.

Abortion, Induced↗
PubMed1989

Innervation of the spleen in the rat: evidence for absence of afferent innervation.

Catecholaminergic fibers in the spleen have been well characterized in the rat and this innervation is believed to be an important source of modulation of the immune system. The presence or role of afferent feedback from the spleen has not been systematically investigated. We have examined whether the spleen receives afferent innervation from sensory ganglia and also have assessed the sources of efferent innervation to the spleen in the rat. The fluorescent retrograde anatomical tracers fluoro-gold (FGo) or fast blue (FB) were injected into the spleens of adult female rats and dorsal root, sympathetic chain, nodose, and celiac-mesenteric plexus ganglia were collected. In additional animals, the spleen was either injected with the anatomical tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP) or else regular HRP was applied to the cut end of the splenic nerve. Also, we examined the effects of cutting the splenic nerve on the retrograde labeling of cell bodies in the ganglia and on the catecholamine histochemistry of the spleen. The neuroanatomical results were based primarily upon the tracer FGo and verified that the celiac-mesenteric plexus ganglia provide a major efferent input to the spleen. Furthermore, lower thoracic sympathetic chain ganglia provide an additional and substantial efferent supply to the spleen. Cutting of the splenic nerve prevented retrograde labeling of cell bodies in the celiac-mesenteric plexus ganglia and sympathetic chain ganglia of rats injected with tracers into the spleen and also eliminated catecholamine histofluorescence in the spleen. In terms of afferent labeling, the results with FGo indicated that there were no cell bodies labeled in afferent ganglia following splenic injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Amidines↗
PubMed1989

Origin of noradrenergic innervation of the spleen in rats.

Noradrenergic (NA) sympathetic innervation of the spleen was examined in young adult Sprague-Dawley rats (200-250 g) following surgical removal of the superior mesenteric-celiac ganglia (SM-CG) and/or bilateral transection of the subdiaphragmatic vagus nerve. Sham-operated and unoperated rats served as controls. NA sympathetic innervation of spleens from sham-operated and unoperated controls, and from vagotomized rats, was qualitatively similar, with fibers distributing to the capsule, trabeculae, vasculature, and parenchyma of the white pulp. Complete ganglionic extirpation resulted in almost total denervation of NA fibers in all compartments of the spleen. High-performance liquid chromatography with electrochemical detection (LCEC) for catecholamines (CA) and quantitative morphometry of the density of NA varicosities confirmed these observations. LCEC revealed a greater than 85% depletion of norepinephrine (NE) in the spleen following superior mesenteric-celiac ganglionectomy. Stereological evaluation of NA varicosities with a point counting method revealed a decline of 99% in the volume density of NA terminals that occurred uniformly in all compartments of spleens from ganglionectomized rats. In addition, stereological analysis revealed a loss of total NA varicosities (approximately 31% decrease) in spleens from sham-operated rats. This loss in volume density occurred largely due to a loss in parenchymal fibers (approximately 45% decrease). Bilateral subdiaphragmatic vagotomy blocked the effect on NA innervation produced by the surgical stress of sham operation. Retrograde tracing following injection of either fluorogold or true blue into the spleen, coupled with immunocytochemical localization of tyrosine hydroxylase (TH), demonstrated abundant fluorogold (true blue)-labeled neurons in the SM-CG; many, but not all, of these neurons also were TH-positive. These findings indicate that the SM-CG neurons supply NA innervation to the spleen, providing sympathetic innervation as the second neuron in the classical two-neuron sympathetic chain, and suggest additional non-NA innervation of the spleen as well. This study also suggests that surgical stress of sham operation may alter directly the NA innervation of the spleen, possibly by inducing temporary retraction of NA fibers of the parenchymal compartment, which is likely to reduce the availability of NE for interaction with cells of the immune system that possess adrenoceptors and are present adjacent to NA varicosities in this region.4+ Bilateral vagotomy ameliorated the effects of sham operation on NA innervation; since the vagal nerve does not distribute fibers to the spleen, this effect is likely to occur through altered feedback circuits effecting sympathetic outflow, or through altered neuroendocrine outflow.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic Fibers↗
PubMed2004

[The ultrasound contrast agent levovist helps with the differentiation between accessory spleen and lymph nodes in the splenic hilum: a pilot study].

BACKGROUND: In patients with focal lesions which are isoechogenic to the spleen and which are located next to the spleen it is not easy to differentiate between lymph nodes and the accessory spleen. Therefore, the aim of this study was to evaluate if the color-SAE technique performed after injection of Levovist is able to differentiate between accessory spleens and lymph nodes in patients with a mass in the hilus of the spleen. METHODS: 12 patients with sonographic proof of a hypoechoic mass in the hilus of the spleen were examined (Sonoline-Elegra ultrasound system, Siemens, Erlangen, Germany). Color-SAE was performed 10 minutes after injection of 1 g of Levovist i. v. RESULTS: All patients with accessory spleens (n = 7) showed a color-SAE mosaic pattern in the localization of the mass comparable to the color-SAE mosaic found in the spleen. In contrast, in none of the patients with lymph nodes next to the spleen (n = 5) was a color-mosaic pattern localized to the mass found, wheras the spleen showed regular color-SAE in all cases. CONCLUSION: Color-SAE with Levovist is a new diagnostic tool for the differentiation between accessory spleens and lymph nodes.

Contrast Media↗
PubMed1978

Monoclonal origin of B lymphocyte colony-forming cells in spleen colonies formed by multipotential hemopoietic stem cells.

Spleen colonies produced by transplanting lethally irradiated mice with either 12 day fetal liver or adult bone marrow cells were found to contain B- lymphocyte colony-forming cells (BL-CFC) . The proportion of BL-CFC positive spleen colonies did not increase substantially between 8 and 14 days after transplantation, the range being 18-45 percent. However, the absolute number of BL-CFC per spleen colony varied considerably (between 1 and 10,318), although the majority of colonies contained less than 200 BL-CFC. Irrespective of the time after transplantation, smaller spleen colonies were found to have a higher frequency of BL-CFC than larger spleen colonies. To determine the possible clonal origin of BL-CFC from spleen colony- forming unit (CFU-S), CBA mice were injected with equal numbers of CBA and CBA T(6)/T(6) fetal liver or adult bone marrow cells. Analysis of 7-15-day spleen colonies demonstrated that 90 percent were either exclusively T(6) positive or T(6) negative and approximately equal numbers ofboth colony types were observed. B-lymphocyte colonies were grown and successfully karyotyped from 19 spleen colonies. When compared with the original spleen colony karyotype the B-lymphocyte colony cells karyotype was identical in all 19 cases. In 3 of the 19 colonies analyzed a mixture of T(6) positive and T(6) negative karyotypes was present and identical proportions of the karyotypes were present in the pooled B-lymphocyte colony cells and spleen colony cells. The data indicate that the B-lymphocyte colony-forming cells detected in spleen colonies are genuine members of the hemopoietic clone derived from the initiating hemopoietic stem cell (CFU-S).

Animals↗
PubMed1972

Responses of the isolated, perfused human spleen to sympathetic nerve stimulation, catecholamines and polypeptides.

1. The responses of the smooth muscle of the capsule and blood vessels of the isolated, perfused human spleen to sympathetic nerve stimulation, adrenaline, noradrenaline, angiotensin, oxytocin, vasopressin, isoprenaline and acetylcholine have been investigated and compared with those of dog spleen.2. Stimulation of the postganglionic sympathetic nerves to the human spleen at frequencies of 3-10 Hz evoked graded vasoconstriction but very small changes in spleen volume.3. The injection of adrenaline and noradrenaline in doses of 0.25-25 mug to the human spleen produced graded increases in splenic vascular resistance with very small decreases in spleen volume.4. Administration of the alpha-adrenoceptor blocking drug phenoxybenzamine completely abolished or considerably reduced the vascular responses of the human spleen to sympathetic nerve stimulation or the injection of noradrenaline.5. The vascular action of adrenaline was often reversed to elicit a vasodilatation after phenoxybenzamine suggesting the presence of beta-adrenoceptors in the vascular bed. This was confirmed by the administration of isoprenaline which induced a marked reduction in vascular resistance of the human spleen.6. The polypeptides angiotensin and vasopressin induced a marked vasoconstriction in the human spleen without changes in the spleen volume. These effects were uninfluenced by the administration of phenoxybenzamine.7. The polypeptide oxytocin caused a slight vasodilatation in the human spleen, an effect almost exactly mimicked by the preservative chlorobutanol.8. Preliminary experiments suggest that noradrenaline is the transmitter released by the postganglionic nerves to the human spleen.9. These results provide direct evidence that the normal human spleen, unlike that of the dog, does not have a reservoir function. It is suggested that contractions of the enlarged human spleen may occur in various pathological conditions.

Acetylcholine↗
PubMed1983

Prediction of spleen size by routine radioisotope scintigraphy.

Technetium-99m scintigraphy of the spleen was performed in 32 patients with various haematologic disorders prior to splenectomy. From the gamma camera image of the spleen, the weight of the spleen was estimated using two different mathematical formulas, and the results obtained were compared to the postoperative spleen weight. Both formulas revealed spleen weights showing highly significant correlations to the postoperative spleen weight and with similar standard deviations. Visual evaluation of the scintigram by an experienced examiner with classification of the spleens into four groups according to spleen weight revealed results as good as the mathematical calculations in predicting the postoperative spleen weight, both techniques giving diagnostic specificities of 0.70-0.80 for all groups and diagnostic sensitivities of 0.80-1.00. Physical examination of the abdomen showed that about 50% of the spleens weighing between 250 and 1,000 g were not palpable. Therefore, it is concluded that physical examination of the abdomen alone is unreliable. Radioisotope scintigraphy of the spleen is recommended, this method being fast, with negligible discomfort to the patient, and with sufficient accuracy for daily clinical work.

Adult↗
PubMed2002

Spleen lymphocyte kinetics in mice under normal and inflammatory conditions: an application of the transgenic mouse expressing beta-galactosidase (ROSA 26).

The purpose of this study was to develop a method for the measurement of the cell kinetics of spleen lymphocytes using the ROSA 26 transgenic mouse ubiquitously expressing beta-galactosidase (beta-gal). Spleen lymphocytes were isolated from ROSA 26 mice and intravenously inoculated into C57BL/6 mice under normal conditions and inflammatory conditions following lipopolysaccharide (LPS) treatment. Spleen lymphocyte accumulation in tissues was determined as a measurement of beta-gal activity. Spleen lymphocytes isolated from ROSA 26 mice have beta-gal activities of 1.45 x 10(-4) pg per cell. A good correlation between beta-gal activities and cell numbers was obtained (r2 = 0.999) over the range 1 x 10(3) to 1 x 10(7) cells, corresponding to 70 fg to 350 pg beta-gal activity. Spleen lymphocytes (4 x 10(7) cells) were intravenously inoculated into normal mice and subsequently each tissue was isolated and the corresponding beta-gal activity measured. Spleen lymphocyte accumulation was relatively high .in the spleen and lymph nodes. The accumulated spleen lymphocyte cell number was 1.39 x 10(7) cells/g spleen and 5.45 x 10(7) cells/g lymph node 1 h and 6h after inoculation, respectively, and this remained constant up to 24h. In the lung, lymphocyte accumulation was 3.98 x 10(7) cells/g tissue 10 min after inoculation then gradually fell to 7.09 x 10(5) cells/g tissue after 24h. In addition, the femoral muscle following intramuscular injection of LPS showed a high accumulation of spleen lymphocytes, whereas the untreated and contralateral femoral muscle had the same level as the background. In conclusion, spleen lymphocytes isolated from ROSA 26 mice can be used to measure beta-gal activity and the sensitivity is relatively high over the 70 fg to 350 pg range. This suggests that cells isolated from the ROSA 26 mouse can be applied to the study of cell kinetics.

Animals↗
PubMed1993

Volume of the spleen in children as measured on CT scans: normal standards as a function of body weight.

OBJECTIVE: The purpose of this study was to develop standards for the normal volume of the spleen in children as measured on CT scans. SUBJECTS AND METHODS: CT scans were used to measure the volume of the spleen in 48 children (30 boys and 18 girls), 1 day to 18 years old (mean and median ages were 8.2 and 7.8 years, respectively). Children who had underlying malignant tumors, infection, hematologic diseases, or other conditions that could alter splenic size were excluded. The area of the spleen on each axial section was determined by tracing its outline on the CT monitor and measuring the area of the region of interest. The area of the spleen on each section was multiplied by the slice thickness to calculate the volume of the spleen for each section. The total volume of the spleen was then determined by adding the individual volumes for each of the sections through the spleen. This method of calculating splenic volume has been validated in previous studies in adult subjects. The volume of the spleen was analyzed as a function of both body weight and age. RESULTS: The volume of the spleen correlated better with body weight than with age. The best regression model (r = .85) was a linear relationship as follows: splenic volume (cm3) = 0.7 + [4.6 x weight (kg)]. Using these data and a regression model, we generated standards for normal volume of the spleen as a function of body weight (with 95% tolerance intervals). CONCLUSION: We have developed CT standards for normal splenic volume in children. These standards can be used to objectively measure the size of the spleen in children who have clinically suspected splenomegaly.

Body Weight↗
PubMed2005

Sonographic evaluation of spleen size in tall healthy athletes.

OBJECTIVE: The purpose of this study was to establish the range of spleen sizes in tall healthy athletes. SUBJECTS AND METHODS: Sonographic measurements of spleen size and left renal length were performed on 129 college athletes (82 men, 47 women). Length, width, and thickness of the spleen and left renal length were obtained. In addition, the height, weight, and age of each athlete were recorded. Pearson's product moment correlation coefficients were calculated, and linear regression analysis was used to create a model for calculating normative values. RESULTS: The mean body height for men was 74.3 (189 cm) +/-(SD) 3.7 inches (9 cm) and for women was 69.3 (176 cm) +/- 3.7 inches (9 cm). Spleen length was greater than 12 cm in 31.7% of the men (mean spleen length, 11.4 +/- 1.7 cm) and in 12.8% of the women (mean spleen length, 10.3 +/- 1.3 cm). In women, height correlated with spleen length (r = 0.3, p = 0.05), width (r = 0.4, p = 0.01), and volume (r = 0.3, p = 0.02) but not with thickness (r = 0.08, p = 0.6). Spleen length did correlate with left renal length (r = 0.5, p = 0.0005). In men, height correlated with spleen length (r = 0.4, p = 0.0003), width (r = 0.5, p = 0.0001), and volume (r = 0.4, p = 0.0002) and less with thickness (r = 0.3, p = 0.01). Spleen length and left renal length were poorly correlated (r = 0.2, p = 0.04). Regression analysis showed that in women taller than 5 ft 6 inches (168 cm), the mean splenic length of 10 cm increased by 0.1 cm for each 1-inch incremental increase in height. In men taller than 6 ft (180 cm), the mean splenic length of 11 cm increased by 0.2 cm for each 1-inch incremental increase in height. CONCLUSION: Spleen size correlates with height in tall healthy athletes. Nomograms from this data can be used to gauge the risk of returning to play after episodes of acute splenomegaly, as with infectious mononucleosis.

Adult↗
PubMed1992

Different subsets of T cells in the adult mouse bone marrow and spleen induce or suppress acute graft-versus-host disease.

Fractionation of normal adult mouse spleen and bone marrow cells (C57BL/Ka) was performed by discontinuous Percoll density gradients. The fractionated low density (1.050-1.060 g/ml) C57BL/Ka spleen cells completely suppressed acute lethal graft vs host disease (GVHD) when coinjected with unfractionated C57BL/Ka spleen cells into sublethally irradiated (400 rad) BALB/c mice. In dose response experiments, as few as 0.5 x 10(6) low density cells from the spleen fractions suppressed acute GVHD induced by 2.5 x 10(6) unfractionated allogeneic spleen cells. Although the low density spleen fractions inhibited acute GVHD, the high density (1.075-1.090 g/ml) spleen fractions induced acute GVHD in sublethally irradiated BALB/c recipients. Fractionation of C57BL/Ka bone marrow cells showed that none of the high or low density fractions or unfractionated cells induced lethal GVHD. When these fractions were tested for their capacity to suppress GVHD by coinjection with C57BL/Ka unfractionated spleen cells, all fractions protected the BALB/c recipients. Unfractionated bone marrow cells showed modest protection. Evaluation of the dose response characteristics of the suppressive activity of the low and middle density (1.060-1.068 g/ml) bone marrow cell fraction showed that reproducible protection could be achieved at a 5:1 ratio of inducing to suppressing cells. The low density fractions of both bone marrow and spleen cells had a marked depletion of typical TCR(+)-alpha beta CD4+ or CD8+ T cells, and a predominant population of TCR(+)-alpha beta CD4- CD8- T cells. Purified populations of the latter cells suppressed GVHD. Recipients given unfractionated C57BL/Ka spleen cells and protected with low-density bone marrow or spleen cells were chimeras.

Animals↗
PubMed1989

[Spleen and hematopoiesis].

In order to investigate the role of the human spleen on hematopoiesis, hematopoietic stem cells and stimulates were evaluated in fetal and adult spleens. BFU-E and CFU-C were existed in 20 weeks and 23 weeks fetal spleens (BFU-E 145 +/- 45/10(5) mononuclear cells, CFU-C 55 +/- 6/10(5) mononuclear cells). In adult spleen, a few stem cells were recognized, which may be contaminated from peripheral blood in sinus of the spleen. We tested conditioned media from adult spleen cells for the stimulative activity on the in vitro growth of BFU-E and CFU-C from bone marrow mononuclear cells. Spleen conditioned medium stimulated proliferation of these precursor cells. It seemed that PHA-stimulated spleen conditioned medium augmented BFU-E, whereas CFU-C growth was suppressed. Adult and fetal spleens were studied immunohistochemically using anti-G-CSF, GM- CSF and erythropoietin antibodies. The cells with G-CSF and GM-CSF were shown in fetal spleens. In adult spleens, however, only GM-CSF was detected.

Adult↗
PubMed1986

Differential expression of HLA class II antigens in fetal human spleen: relationship of HLA-DP, DQ, and DR to immunoglobulin expression.

Frozen sections of human fetal spleen from 12 to 20 wk gestation were examined by using polyclonal antibodies to Ig isotypes, monoclonal antibodies to HLA class II subregion locus products, B and T cells, and follicular dendritic cells. Scattered lymphoid cells in spleen sections from fetuses of 12 to 13 wk gestational age expressed IgM but not IgD. The appearance of lymphoid cells expressing IgD occurred at 14 to 15 wk before the formation of loose clusters of B cells at 16 wk. IgD expression was associated mainly with cells in these clusters, which by 17 wk had become definite follicles. Follicular dendritic cells were not detectable until 20 wk. OKT3-positive T cells were not detected until 17 wk, and at 20 wk constituted 5% of the nucleated cell population. HLA-DR- and DP-positive lymphocytes and macrophages were detectable in fetal spleen from 12 wk onward; DR was expressed on more cells than DP, and the numbers of cells stained by HLA-DR-specific monoclonal antibodies exceeded the number of Ig-positive cells in all spleens examined. HLA-DQ was expressed by consistently fewer cells than HLA-DR and -DP in all spleens tested. The small number of DQ-positive cells in spleens from 12- to 13-wk fetuses had the morphology of macrophages; HLA-DQ expression by lymphoid cells followed a similar pattern to IgD expression and was associated mainly with follicular lymphocytes. It could be demonstrated by double-labeling experiments that all follicular IgM-positive cells in 17- to 20-wk spleens expressed HLA-DP, DQ, and DR antigens: IgM-positive cells in 12- to 16-wk spleens and interfollicular IgM-positive cells in 17- to 20-wk spleens all expressed HLA-DR, but only 59% and 43% expressed DP and DQ, respectively. Ninety-one to 100% of IgD-positive cells in all spleens examined expressed HLA-DQ in addition to DR and DP. In these experiments IgD-negative, DQ-positive cells had the morphologic appearance characteristic of macrophages. These data suggest that class II antigens are differentially expressed on developing lymphoid cells; DR and DP expression occurring in the earliest spleens examined, with expression of DP on a subpopulation of DR-positive cells; IgD and DQ expression appears to be coincident on maturing B cells as they begin to form follicles. An immunoregulatory role for HLA-DQ in B cell development is implicated and remains to be fully investigated.

Antibodies, Monoclonal↗