Rap1 Is Essential for B-Cell Locomotion, Germinal Center Formation and Normal B-1a Cell Population.

Integrin regulation by Rap1 is indispensable for lymphocyte recirculation. In mice having B-cell-specific Rap1a/b double knockouts (DKO), the number of B cells in lymph nodes decreased to approximately 4% of that of control mice, and B cells were present in the spleen and blood. Upon the immunization with NP-CGG, DKO mice demonstrated the defective GC formation in the spleen, and the reduced NP-specific antibody production. In vitro, Rap1 deficiency impaired the movement of activated B cells along the gradients of chemoattractants known to be critical for their localization in the follicles. Furthermore, B-1a cells were almost completely absent in the peritoneal cavity, spleen and blood of adult DKO mice, and the number of B-cell progenitor/precursor (B-p) were reduced in neonatal and fetal livers. However, DKO B-ps normally proliferated, and differentiated into IgM+ cells in the presence of IL-7. CXCL12-dependent migration of B-ps on the VCAM-1 was severely impaired by Rap1 deficiency. Immunostaining study of fetal livers revealed defects in the co-localization of DKO B-ps and IL-7-producing stromal cells. This study proposes that the profound effects of Rap1-deficiency on humoral responses and B-1a cell generation may be due to or in part caused by impairments of the chemoattractant-dependent positioning and the contact with stromal cells.

Comparison of Macrophage Activation Using γ-Globulin and Serum-derived Macrophage Activating Factor.

BACKGROUND/AIM: Serum-derived macrophage activating factor (serum-MAF) can rapidly activate macrophage phagocytic activity by inducing characteristic membrane ruffles designated as Frill-like structures. Serum-MAF contains γ-globulin, an activator of phagocytosis. This study examined whether serum-MAF and γ-globulin activate macrophages similarly. MATERIALS AND METHODS: Morphological changes in macrophages were observed by time-lapse imaging and the efficiency of engulfment was analysed quantitatively. Immunological staining of talin-1 and a calpain inhibitor were performed. RESULTS: The engulfment efficiency of serum-MAF- and γ-globulin-activated macrophages was significantly different. Talin-1 showed weak co-localisation with the Frill-like structures. Treatment with a calpain inhibitor similarly down-regulated phagocytosis irrespective of the activation factor. CONCLUSION: There was a difference between macrophage activation mechanisms by γ-globulin and serum-MAF. Talin may slightly contribute to serum-MAF activation. It is possible to distinguish between the calpain-dependent fundamental 'mechanism of phagocytosis' and the activating factor-dependent rapid 'activation mechanism'.

Curative effects of vancomycin and cefotaxime combined with gamma globulin respectively in neonatal septicemia and their influences on PCT, CRP and hs-CRP.

OBJECTIVE: To explore the curative effects of vancomycin and cefotaxime combined with gamma globulin respectively in neonatal septicemia and their influences on PCT, CRP, and hs-CRP, so as to provide references for clinical treatment. PATIENTS AND METHODS: 181 patients with neonatal septicemia admitted to Huangshi Maternity and Child Health Hospital from April 2012 to August 2014 were selected as the study subjects. Patients treated with vancomycin combined with gamma globulin were selected as group A (96 cases) and those treated with cefotaxime combined with gamma globulin were selected as group B (85 cases). The improvement time of clinical symptoms (milk rejection, nervous system symptoms, body temperature), hospital stays, mortality, medicine curative effects, adverse reactions, complications, and levels of serum CRP, PCT, and hs-CRP of patients before and after treatment were compared between the two groups. RESULTS: The improvement time of clinical symptoms like body temperature, milk rejection, and neurological symptoms, as well as hospital stays in group A were lower than those in group B (p<0.05); the total effective rate of medicine curative effects in group B was better than that in group A (p<0.05); there was no significant difference in levels of serum CRP, PCT, and hs-CRP between the two groups before treatment (p>0.05); after treatment, levels of serum CRP, PCT, and hs-CRP in both groups decreased significantly, and levels of serum CRP, PCT, and hs-CRP in group B decreased more significantly than those in group A (p<0.05). CONCLUSIONS: Cefotaxime combined with gamma globulin in the treatment of patients with neonatal septicemia has short improvement time in clinical symptoms, high total effective rate of drugs, low mortality, fewer adverse reactions and complications, and can significantly reduce levels of serum CRP, PCT, and hs-CRP, which is worthy of further promotion and application in clinical practice.

Insights to the Binding of a Selective Adenosine A3 Receptor Antagonist Using Molecular Dynamic Simulations, MM-PBSA and MM-GBSA Free Energy Calculations, and Mutagenesis.

Adenosine A3 receptor (A3R) is a promising drug target cancer and for a number of other conditions like inflammatory diseases, including asthma and rheumatoid arthritis, glaucoma, chronic obstructive pulmonary disease, and ischemic injury. Currently, there is no experimentally determined structure of A3R. We explored the binding profile of O4-{[3-(2,6-dichlorophenyl)-5-methylisoxazol-4-yl]carbonyl}-2-methyl-1,3-thiazole-4-carbohydroximamide (K18), which is a new specific and competitive antagonist at the orthosteric binding site of A3R. MD simulations and MM-GBSA calculations of the WT A3R in complex with K18 combined with in vitro mutagenic studies show that the most plausible binding conformation for the dichlorophenyl group of K18 is oriented toward trans-membrane helices (TM) 5, 6 and reveal important residues for binding. Further, MM-GBSA calculations distinguish mutations that reduce or maintain or increase antagonistic activity. Our studies show that selectivity of K18 toward A3R is defined not only by direct interactions with residues within the orthosteric binding area but also by remote residues playing a significant role. Although V1695.30 is considered to be a selectivity filter for A3R binders, when it was mutated to glutamic acid, K18 maintained antagonistic potency, in agreement with our previous results obtained for agonists binding profile investigation. Mutation of the direct interacting residue L903.32 in the low region and the remote L2647.35 in the middle/upper region to alanine increases antagonistic potency, suggesting an empty space in the orthosteric area available for increasing antagonist potency. These results approve the computational model for the description of K18 binding at A3R, which we previously performed for agonists binding to A3R, and the design of more effective antagonists based on K18.

Immune Complexes Impaired Glomerular Endothelial Cell Functions in Lupus Nephritis.

Lupus nephritis (LN) is one of the most common and severe complications of lupus. However, the mechanisms for renal damage have not been well elucidated. There are evidences show that glomerular endothelial cells (GECs) are damaged in LN. Immune complexes can deposit in subendothelial area and could affect GEC functions. In the present study, we used heat-aggregated gamma globulin (HAGG) to simulate immune complexes and investigated their effects on GEC functions. Our results revealed that HAGG impaired different aspect of the GEC functions. HAGG changed cell morphology, upregulated the expression of active caspase-3, inhibited angiogenesis, and increased NO production in GECs. These results provide new clues for the mechanisms of renal damage and the pathology of LN.

Effect of glucocorticoid combined with gamma globulin in treatment of children with myasthenia gravis and its effects on immune globulin and complement of children.

OBJECTIVE: To discuss the effects glucocorticoid combined with gamma globulins in the treatment of children with myasthenia gravis and its effects on immune globulin and complement of children. PATIENTS AND METHODS: Clinical data of 70 cases of childhood myasthenia gravis in this hospital were retrospectively analyzed. These cases were randomly divided into observation group and control group. For observation group, there were methylprednisolone and gamma globulins while the only methylprednisolone in the control group. The clinical effects and changes in immune globulin and complement of two groups were observed. RESULTS: The total effective rate for observation group was 94.3% and 74.3% for the control group, and this difference was statistically significant (p < 0.05) The time for relief of symptoms (6.55 ± 1.35 days) and total hospital stay (17.15 ± 3.65 days) in observation group was apparently shorter than the control group, with statistical significance (p < 0.05). CONCLUSIONS: Glucocorticoid and gamma globulin can improve the symptoms and achieve satisfying clinical effects for the treatment of myasthenia gravis in children. Thus, it is valuable for further popularization and application.

[INHIBITION OF GROWTH OF BACTERIA IN STAPHYLOCOCCUS AUREUS AND PSEUDOMONASAERUGINOSA CULTURES BY COPPER AND ZINC CATIONS, APPLIED AT PHYSIOLOGICAL CONCENTRATIONS].

AIM: Evaluation of antibacterial effect,of γ-globulin fraction bound and free copper and zinc cations, applied in cultures-of S. aureus and P. aeruginosa at physiological (micromolar) concen- trations. MATERIALS AND METHODS: Day cultures of S. aureus or P. aeruginosa were transferred from agar to physiological solution, and cell suspension was prepared, containing approximately 10 - 101 CFU/ml. Samples of metal-complexes of γ-globulin.with copper and zinc cations (30 and 45 µg/ml),. control γ-globulins (30 and 45 µg/ml) and salt solutions of copper and zinc, cation content in those corresponded to the quantity of the metal, that had bound with the protein at the stage of metal-complex obtaining (75 ng/ml), were introduced into the suspension. The suspensions were incubated at 37°C for 6 hours, sampling and CFU count according to the accepted micromethod was carried out every 2 hours. By the end of incubation (6 hours of observation) the suspensions were transferred into nutrient broth, thermostated for 1 day at 37°C, transparency of the nutrient broth compared with control (sterile) was evaluated afterwards. RESULTS: Toxic effect of copper and zinc cations is detected starting from the 3rd hour of observation in S. aureus culture. Viable bacteria are absent in the culture with zinc after 6 hours, with copper - after 4 hours of incubation. γ-globulin, that had bound copper cations, reduces the quantity ofviable cells compared with control protein by 11.9 - 33.0% (p<0.05 - 0.1) at 4 and 6 hours of incubation. In P. aeruginosa culture, toxic effect of copper. cations manifests immediately after initiation of the culture and results in realization of complete bactericidal effect after 4.hours of observation. Zinc cations do not have such properties. γ-globulin, that had bound copper cations, reduces the quantity of viable cells compared with control protein at 4 and 6 hours ofincubationby 19.3- 25.8% (p<0.00 1). CONCLUSION: S. aureus bacteria, supported in physiological solution are subject to toxic effect of physiological'(micromolar) concentrations of free copper and zinc cations, and also copper cations, bound by human serum γ-globulin. P. aeruginosa bacteria under the same conditions.experience toxic effect of copper cations (but not zinc), free as well as bound by human serum γ-globulin. Whereas a full bactericidal effect is realized in S. aureus and P. aeruginosa cultures in the-presence of free cations of copper.

Use of Gammaglobulin to Lower Elevated Natural Killer Cells in Patients with Recurrent Miscarriage.

OBJECTIVE: To evaluate the effectiveness of intravenous immunoglobulin (IVIG) in patients presenting with recurrent miscarriage and abnormally elevated natural killer (NK) cells. STUDY DESIGN: This retrospective patient controlled evidence level II-2 pilot study was conducted at Cohen Center, P.A., Medical City Dallas Hospital. Ninety women with a history of recurrent miscarriage (average, 5) and elevated NK cells were retrospectively evaluated to document the outcome of their treatment with IVIG. RESULTS: Of 90 women with elevated NK cells who received IVIG treatment, 78 (86.7%) became pregnant. Sixty-four (82.0%) of those pregnancies had a successful viable outcome. Fourteen (18.0%) gestations ended as first trimester miscarriages. CONCLUSION: We conclude at evidence level II-2 that, with adequate precautions, low-dose IVIG therapy is safe and effective for women with immunologic abortion and documented abnormally elevated NK cells.

Effects of hyaluronic acid and γ-globulin concentrations on the frictional response of human osteoarthritic articular cartilage.

Synovial fluid plays an important role in lubricating synovial joints. Its main constituents are hyaluronic acid (HA) and γ-globulin, acting as boundary lubricants for articular cartilage. The aim of the study was to demonstrate the concentration-dependent effect of HA and γ-globulin on the boundary-lubricating ability of human osteoarthritis (OA) cartilage. Normal, early and advance stage articular cartilage samples were obtained from human femoral heads and in presence of either HA or γ-globulin, cartilage frictional coefficient (µ) was measured by atomic force microscopy (AFM). In advanced stage OA, the cartilage superficial layer was observed to be completely removed and the damaged cartilage surface showed a higher µ value (∼ 0.409) than the normal cartilage surface (∼ 0.119) in PBS. Adsorbed HA and γ-globulin molecules significantly improved the frictional behavior of advanced OA cartilage, while they were ineffective for normal and early OA cartilage. In advanced-stage OA, the concentration-dependent frictional response of articular cartilage was observed with γ-globulin, but not with HA. Our result suggested that HA and γ-globulin may play a significant role in improving frictional behavior of advanced OA cartilage. During early-stage OA, though HA and γ-globulin had no effect on improving frictional behavior of cartilage, however, they might contribute to disease modifying effects of synovial fluid as observed in clinical settings.

Toll-like receptor 9 signaling acts on multiple elements of the germinal center to enhance antibody responses.

Recent studies have demonstrated important roles of nucleic acid-sensing Toll-like receptors (TLRs) in promoting protective antibody responses against several viruses. To dissect how recognition of nucleic acids by TLRs enhances germinal center (GC) responses, mice selectively deleted for myeloid differentiation primary-response protein 88 (MyD88) in B cells or dendritic cells (DCs) were immunized with a haptenated protein antigen bound to a TLR9 ligand. TLR9 signaling in DCs led to greater numbers of follicular helper T (TFH) cells and GC B cells, and accelerated production of broad-affinity antihapten IgG. In addition to modulating GC selection by increasing inducible costimulator (ICOS) expression on TFH cells and reducing the number of follicular regulatory T cells, MyD88-dependent signaling in B cells enhanced GC output by augmenting a class switch to IgG2a, affinity maturation, and the memory antibody response. Thus, attachment of a TLR9 ligand to an oligovalent antigen acted on DCs and B cells to coordinate changes in the T-cell compartment and also promoted B cell-intrinsic effects that ultimately programmed a more potent GC response.

[Comparison of the effects of glutamate antibodies on neuronal activity of caspase 3 and memory impairment in rats induced by injection of Abeta(25-35) into the Meynert nuclei].

In experiments on rats showed that intranasal administration of glutamate antibodies in a dose of 300 microg/kg after 1 h after bilateral injection of neurotoxic fragment of beta-amyloid protein (25-35)--Abeta(25-35)--into the Meynert nuclei restores learning ability in the test of passive avoidance on 3 and 14 days of the experiment. Antibodies to glutamate decrease significantly increasing caspase 3 activity, detected on Day 3 after injection of Abeta(25-35), in samples of the prefrontal cortex and hippocampus but not hypothalamus. Intranasal administration of gamma-globulin had no effect on the performance of violations of mnestic functions and caspase 3 activity.

Soluble immune complexes shift the TLR-induced cytokine production of distinct polarized human macrophage subsets towards IL-10.

BACKGROUND: Costimulation of murine macrophages with immune complexes (ICs) and TLR ligands leads to alternative activation. Studies on human myeloid cells, however, indicate that ICs induce an increased pro-inflammatory cytokine production. This study aimed to clarify the effect of ICs on the pro- versus anti-inflammatory profile of human polarized macrophages. MATERIALS AND METHODS: Monocytes isolated from peripheral blood of healthy donors were polarized for four days with IFN-γ, IL-4, IL-10, GM-CSF, M-CSF, or LPS, in the presence or absence of heat aggregated gamma-globulins (HAGGs). Phenotypic polarization markers were measured by flow cytometry. Polarized macrophages were stimulated with HAGGs or immobilized IgG alone or in combination with TLR ligands. TNF, IL-6, IL-10, IL-12, and IL-23 were measured by Luminex and/or RT-qPCR. RESULTS: HAGGs did not modulate the phenotypic polarization and the cytokine production of macrophages. However, HAGGs significantly altered the TLR-induced cytokine production of all polarized macrophage subsets, with the exception of MΦ(IL-4). In particular, HAGGs consistently enhanced the TLR-induced IL-10 production in both classically and alternatively polarized macrophages (M1 and M2). The effect of HAGGs on TNF and IL-6 production was less pronounced and depended on the polarization status, while IL-23p19 and IL-12p35 expression was not affected. In contrast with HAGGs, immobilized IgG induced a strong upregulation of not only IL-10, but also TNF and IL-6. CONCLUSION: HAGGs alone do not alter the phenotype and cytokine production of in vitro polarized human macrophages. In combination with TLR-ligands, however, HAGGs but not immobilized IgG shift the cytokine production of distinct macrophage subsets toward IL-10.

Effect of protein concentrations of bovine serum albumin and γ-globulin on the frictional response of a cobalt-chromium femoral head.

The study aims to identify the concentration-dependent role of bovine serum albumin (BSA) and γ-globulin in the lubricating ability of a cobalt-chromium femoral head. The frictional coefficients of the cobalt-chromium femoral head decreased with increasing BSA concentrations from 10 to 40 mg/ml and showed statistical differences between any of the BSA concentration groups, except between the 30 and 40 mg/ml concentration groups. In γ-globulin, the frictional coefficients significantly decreased at concentrations of 2.5 and 5.0 mg/ml as compared with the PBS control group, but significant increases were observed at 7.5 and 12.5 mg/ml. These results suggest that the friction of the cobalt-chromium femoral head is dependent on the concentration of both BSA and γ-globulin. However, there is a maximum concentration for BSA to act as an effective boundary lubricant, while the lubricating ability of γ-globulin is most effective in the physiological concentration range within human synovial fluid.

A novel anti-peroxiredoxin autoantibody in patients with Kawasaki disease.

Antibodies to the anti-oxidative peroxiredoxin (Prx) enzymes occur in both systemic autoimmune disease and vasculitis in adulthood. Because increased oxidative stress induces vasculitis in Kawasaki disease (KD), autoimmunity to Prxs in patients with KD was investigated. The presence of antibodies to Prx 1, 2 and 4 was analyzed by ELISA and Western blot. Of 30 patients with KD, 13 (43.3%) possessed antibodies to Prx 2, whereas these antibodies were present in only 1 of 10 patients (10.0%) with sepsis (4 with purulent meningitis and 6 with septicemia). In contrast, antibodies to Prx 1 and 4 were not detected in either group. There was no significant correlation among the titers of the three antibodies. Clinical parameters were compared between anti-Prx 2-positive and -negative patients. The presence of anti-Prx 2 antibodies correlated with a longer period of fever and poor response to high-dose γ-globulin therapy in patients with KD. Anti-Prx 2-positive patients had significantly greater excretion of urinary 8-isoprostaglandin than did anti-Prx 2-negative patients. These results provide the first evidence for an antibody to Prx 2 in patients with KD. They also suggest that this antibody might serve as a marker of disease severity and be involved in the pathophysiology of vasculitis in some patients with KD.

Acceso a medicamentos: impacto de la diferencia de precios de distintas marcas de Gammaglobulina Endovenosa (GGEV) en el presupuesto hospitalario / Access to drugs: impact of the costs of different brands of intravenous gammaglobulin (IVIG) on the hospital budget

Calcular y analizar la diferencia de costos registrada en las compras de gammaglobulina endovenosa realizadas durante el período 1998-2002, entre las marcas adquiridas y la marca actualmente en uso. Evaluar su impacto en el presupuesto establecido para la compra de medicamentos de la institución. Material y métodos: Se realizó un estudio de costos retrospectivo, comparando los precios de las gammaglobulinas adjudicadas entre los años 1998-2002, con los de la marca que se encuentra en uso desde el año 2003: GGEV del Laboratorio Hemoderivados de Universidad de Córdoba (LHUNC). Las variables estudiadas fueron costos de cada marca de GGEV, Costos anuales de GGEV y Presupuestos anuales de medicamentos por año. Para el cálculo del período 1998-2000 se estimó el precio de la GGEV de LHUNC, realizando un análisis del peor escenario, por falta de registros anteriores al 2000. Resultados: La diferencia de costo total abonada en el período 1998-2002, debido a la compra de GGEV de marcas importadas en lugar de aquella proveniente de la LHUNC, fue de $ 418210.6 (36.5%). Esta diferencia representó un 1.5% aproximadamente del gasto de medicamentos de la institución. Conclusiones: Las compras de gammaglobulina realizadas en el período estudiado generaron un gasto extra innecesario, con un gran impacto sobre el presupuesto de la institución, y por consiguiente, sobre la compra de otros medicamentos. Las decisiones tomadas impidieron el acceso a otros medicamentos esenciales o bien generaron un acceso restringido por falta de presupuesto...

Production of late IFN-α induced by plasma γ-globulin fraction proteins and their metal complexes.

Plasma γ-globulin fraction proteins, copper and zinc cations, and metal complexes they form with human serum γ-globulin induce the production of IFN-α by human blood cells throughout the periods of up to 72 h. Zinc cation-modified protein by 1.6 times (p<0.05) more actively induces late IFN-α than the control γ-globulin; γ-globulin-copper metal complex is 2-fold (p<0.002) more effective than the control protein. The results indicate that functional relationships between the components inducing the production of late IFN-α differ from the effects realized during the early period of induction.

Detection of IFN-alpha produced in the presence of plasma gamma-globulin fraction proteins.

Interferon-alpha was detected in IFN pool produced by human leukocytes in the presence of gamma-globulin fraction proteins, copper and zinc cations, and metal-modified gamma-globulins. The cytokine appeared in culture medium at early terms (24 h) of incubation, is characterized by acid resistance, and is neutralized by antibodies to IFN-alpha. The content of IFN-alpha in supernatants of induced leukocytes reached 60-90 pg/ml and correlated with antiviral activity of the samples. Zinc bound to human serum gamma-globulin attenuated and copper stimulated the realization of IFN-inducing characteristics of the protein at early terms of incubation.

Induction of interferon production by conformation-modified proteins of plasma gamma-globulin fraction.

Plasma gamma-globulin fraction proteins, copper and zinc cations, and metal-modified gamma-globulins induce the production of IFN by human leukocytes. Binding of zinc cations attenuates the realization of the IFN-inducing effects of human serum gamma-globulin, while binding of copper cations potentiated this effect. Activity of IFN and the dynamics of its production correspond to those in response to phytohemagglutinin stimulation. The pool of induced IFN contains acid-labile (up to 60%) and acid-stable (up to 40%) constituents. Anti-IFN-alpha antibodies do not modify activity of produced IFN. The results indicate the possibility of gamma-globulin conformation allowing stimulation or attenuation of the protein capacity to induce the production of IFN pool with predominant content of IFN-gamma.

Management and outcome of intravenous gammaglobulin-resistant Kawasaki disease.

INTRODUCTION: This study aimed to determine the prevalence and risk of intravenous gammaglobulin (IVIG)-resistant Kawasaki disease (KD) and report the outcome of treatment in patients with persistent or recurrent fever. METHODS: 70 KD patients, who received IVIG treatment (2 g/kg) at a tertiary care hospital from January 1995 to June 2004, were retrospectively reviewed. RESULTS: Nine (13 percent) of the 70 patients failed to respond to initial treatment with IVIG. The patients who did not respond to IVIG had higher erythrocyte sedimentation rate (ESR) (104 versus 74 mm/h; p-value is 0.003), longer total days of fever (14.4 +/- 3.8 versus 9.2 +/- 2.3 days; p-value is 0.003) and higher initial coronary artery lesions (CAL) (7 of 9 [77.7 percent] versus 10 of 61 [16.3 percent]; p-value is 0.001) than those who responded to initial treatment. Seven of the nine patients who were retreated with IVIG (2 g/kg) responded to the second dose. The remaining two patients (two of nine, 22 percent) had persistent fever, which subsided after two to three doses of pulse intravenous methylprednisolone. At two months follow-up, IVIG-resistant patients had higher CAL by echocardiogram than IVIG-responsive patients (33 percent versus 3.2 percent, p-value is less than 0.05). Two IVIG-resistant KD patients had delayed diagnosis and developed giant aneurysms. CONCLUSION: Patients with high ESR had increased risk of IVIG-resistant KD. IVIG-resistant Kawasaki patients had a higher prevalence of CAL at the acute phase and two months after onset.

[Preparation of placental-eluted gamma globulin and its immunosuppressive effect in vitro and in vivo].

The aim of this study was to establish a simple, convenient and efficient method of producing placental-eluted gamma globulin (PEGG) from human placenta, explore its inhibitory effect on the function of T lymphocyte in vitro and graft-versus-host disease (GVHD) in vivo. PEGG was prepared by elution at acid pH from human placental tissues that were extensively washed. Its effects on T lymphocyte proliferation induced by PHA and mixed lymphocyte reaction (MLR) were analysed by BrdU ELISA, its effect on the CD25 and CD69 expression on T cells was observed by flow cytometry, and the interferon gamma (IFN-gamma) and interleukin-4 (IL-4) quantification in MLR supernatant were assayed by ELISA. A murine GVHD model was established, the effect of PEGG on the manifestation and pathologic change of GVHD and 45-day survival rate were observed. The results showed that considerable level of immunoglobulin could be eluted from placenta at acid PH, of which the main components were IgG checked by SDS-PAGE analysis. In vitro study indicated that PEGG significantly inhibited both the proliferative response of T cells to PHA and the MLR, down-regulated the expression of CD25 and CD69 on T cells stimulated by PHA, and decreased the secretion of IFN-gamma but increased the production of IL-4 in MLR supernatant. In vivo, recipient mice treated with PEGG had a markedly increased survival rate with less histopathological evidence of GVHD. It is concluded that PEGG can inhibit the proliferation and activation of T cells, regulate the direction of T helper cells differentiating towards Th2 type, and effectively prevent GVHD in a murine model. In short, PEGG may be a potent therapeutic agent for GVHD.