Correlation Between Granulomatous Mastitis and Autoimmune Function and the Immuneregulating Role of Traditional Chinese Medicine

Granulomatous mastitis(GM)is a benign granulomatous condition,and its pathogenesis may be related to autoimmune disorders.Cellular immunity,humoral immunity,immunoglobulins,and complement could all play a role in the disease process,showing certain clinical patterns.Corticosteroids can quickly control disease progression,and immunosuppressants can be used for complex and refractory GM cases.In traditional Chinese medicine(TCM),“healthy qi”is similar to immune system function.For GM with deficient healthy qi,TCM treatments such as internal and external herbal applications can help regulate immune function and shorten disease duration by staged and TCM treatment,regulating viscera,reinforcing healthy qi,and eliminating pathogenic factors.

CTLA-4的研究进展

CTLA 4作为一T细胞活化的负性调节分子 ,在自身免疫性疾病和异种移植排斥过程中起着重要的作用 ,因而受到广泛的注意 ,它不但与Th1 Th2的分化有关 ,还参与T细胞无能的诱导过程 ,其对T细胞活化的抑制作用与其结构功能有着密切的关系。

Assessment and Comparison of in vitro Immunoregulatory Activity of Three Astaxanthin Stereoisomers

In recent years,the immune-modulatory role of all-trans astaxanthin from different pigment sources has been studied.It was reported that all-trans astaxanthin might exist as three stereoisomers,and the composition of all-trans stereoisomers in natural materials differs from that of synthetic products.However,the different biological effects of various all-trans stereoisomers still remain unclear.In the present study,we evaluated the bioactivity of three astaxanthin stereoisomers,(3S,3'S)-trans-,(3R,3'R)-transand meso-trans-astaxanthin,in regulating cell-mediated immune response using mice lymphocytes and peritoneal exudates cells(PECs) systems.After the treatment with three astaxanthin stereoisomers(20 μmol L-1),the lymphocyte proliferation capacity,neutral red phagocytosis of PECs and natural killer(NK) cell cytotoxic activity were comparatively assessed.The results showed that all three astaxanthin stereoisomers significantly promoted lymphocyte proliferation,phagocytic capacity of PECs,and cytotoxic activity of NK cells.Moreover,the(3S,3'S)-trans-astaxanthin exhibited a much higher response than others.

Use of the tumor necrosis factor-blockers for Crohn's disease

The use of anti-tumor necrosis factor-α therapy for inflammatory bowel disease represents the most important advance in the care of these patients since the publication of the National Co-operative Crohn＇s disease study thirty years ago. The recommendations of numerous consensus groups worldwide are now supported by a wealth of clinical trials and several meta-analyses. In general, it is suggested that tumor necrosis factor-c~ blockers （TNFBs） are indicated （1） for persons with moderately-severe Crohn＇s disease or ulcerative colitis （UC） who have failed two or more causes of glucocorticosteroids and an acceptably long cause （8 wk to 12 wk） of an immune modulator such as azathioprine or methotrexate; （2） non-responsive perianal disease; and （3） severe UC not responding to a 3-d to 5-d course of steroids. Once TNFBs have been introduced and the patient is responsive, therapy given by the IV and SC rate must be continued. It remains open to definitive evidence if concomitant immune modulators are required with TNFB maintenance ther- apy, and when or if TNFB may be weaned and discon- tinued. The supportive evidence from a single study on the role of early versus later introduction of TNFB in the course of a patient＇s illness needs to be confirmed. The risk/benefit profile of TNFB appears to be accept- able as long as the patient is immunized and tested for tuberculosis and viral hepatitis before the initiation of TNFB, and as long as the long-term adverse effects on the development of lymphoma and other tumors do not prone to be problematic. Because the rates of ben- efits to TNFB are modest from a population perspec- tive and the cost of therapy is very high, the ultimate application of use of TNFBs will likely be established by cost/benefit studies.

Adenosine:An immune modulator of inflammatory bowel diseases

Inflammatory bowel disease(IBD)is a common and lifelong disabling gastrointestinal disease.Emerging treatments are being developed to target inflammatory cytokines which initiate and perpetuate the immune response.Adenosine is an important modulator of inflammation and its anti-inflammatory effects have been well established in humans as well as in animal models.High extracellular adenosine suppresses and resolves chronic inflammation in IBD models.High extracellular adenosine levels could be achieved by enhanced adenosine absorption and increased de novo synthesis.Increased adenosine concentration leads to activation of the A2a receptor on the cell surface of immune and epithelial cells that would be a potential therapeutic target for chronic intestinal inflammation. Adenosine is transported via concentrative nucleoside transporter and equilibrative nucleoside transporter transporters that are localized in apical and basolateral membranes of intestinal epithelial cells,respectively. Increased extracellular adenosine levels activate the A2a receptor,which would reduce cytokines responsible for chronic inflammation.

From Farming to Engineering： The Microbiota and Allergic Diseases

The steady increase of lgE-dependent allergic diseases after the Second World War is a unique phenomenon in the history of humankind. Numerous cross-sectional studies, comprehensive longitudinal cohort studies of children living in various types of environment, and mechanistic experimental studies have pointed to the disappearance of ＂protective factors＂ related to major changes in lifestyle and environment. A common unifying concept is that of the immunoregulatory role of the gut microbiota. This review focuses on the protection against allergic disorders that is provided by the farming environment and by exposure to microbial diversity. It also questions whether and how microbial bioengineering will be able in the future to restore an interplay that was beneficial to the proper immunological development of children in the past and that was irreversibly disrupted by changes in lifestyle. The protective ＂farming environment＂ includes independent and additional influences： contact with animals, stay in barns/stables, and consumption of unprocessed milk and milk products, by mothers during pregnancy and by children in early life. More than the overall quanti- ty of microbes, the biodiversity of the farm microbial environment appears to be crucial for this protection, as does the biodiversity of the gut microbiota that it may provide. Use of conventional probiotics, especially various species or strains of Lactobacillus and Bifidobacterium, has not fulfilled the expectations of allergists and pediatricians to prevent allergy. Among the specific organisms present in cowsheds that could be used for prevention, Acinetobacter （A.） lwoffii F78, Lactococcus （ L.） lactis G121, and Staphylococcus （S.） sciuri W620 seem to be the most promising, based on experimental studies in mouse models of allergic respiratory diseases. However, the development of a new generation of probiotics based on very productive research on the farming environment faces several obstacles that cannot be overcome without a close collaboration between microbiologists, immunologists, and bioengineers, as well as pediatricians, allergists, specialists of clinical trials, and ethical committees.

Recent advances in cytokines:Therapeutic implications for inflammatory bowel diseases

Inflammatory bowel diseases （IBDs） are complex and chronic disabling conditions resulting from a dysregulated dialogue between intestinal microbiota and components of both the innate and adaptive immune systems. Cytokines are essential mediators between activated immune and non-immune cells, including epithelial and mes- enchymal cells. They are immunomodulatory peptides released by numerous cells and these have significant effects on immune function leading to the differentiation and survival of T cells. The physiology of IBD is becom- ing a very attractive field of research for development of new therapeutic agents. These include cytokines involved in intestinal immune inflammation. This review will focus on mechanisms of action of oytokines involved in IBD and new therapeutic opportunities for these diseases.

Investigation of the Mutagenic Potential of Immunomodulator Arglabin Native in Tablets in the Ames Test

The mandatory preclinical safety evaluation is an essential prerequisite to obtain the qualitative and effective medicines. Due to the fact that drugs may reveal genotoxic properties, the investigation of their mutagenic activity is an obligatory part of the preclinical drug safety program. The aim of the research is to study mutagenic properties of a new original immunomodulator Arglabin native in tablets in the induced test of gene mutations （the Ames test） on Salmonella typhimurium strains. Materials and methods： Four strains of S. typhimurium TA98, TA100, TA1535, and TA1537 were used to assess the mutagenicity in the Ames test. Results and conclusions： No statistically reliable dose-dependent increase in the number of revertant colonies of Salmonella typhimurium has been observed in the presence of the given drug within the investigated dose ranges from 5.0 to 100.0 μg/mL for strains TA100 and TA1535, and from 5.0 to 250 μg/mL for strains TA98 and TA1537 against the baseline of spantaneous mutations. Arglabin native in tablets does not reveal a mutagenic activity within the studied dose ranges on Salmonella typhimurium strains TA98, TA100, TA1535, TA1537.

More stories on Th17 cells

For more than two decades, immunologists have been using the so-called Th1/Th2 paradigm to explain most of the phenomena related to adaptive immunity. The Thl/Th2 paradigm implied the existence of two different, mutu- ally regulated, CD4＋ T helper subsets： Thl cells, driving cell-mediated immune responses involved in tissue damage and fighting infection against intracellular parasites; and Th2 cells that mediate IgE production and are particu- larly involved in eosinophilic inflammation, allergy and clearance of helminthic infections. A third member of the T helper set, IL-17-producing CD4＋ T cells, now called Th17 cells, was recently described as a distinct lineage that does not share developmental pathways with either Thl or Th2 cells. The Th17 subset has been linked to autoimmune disorders, being able to produce IL-17, IL-17F and IL-21 among other inflammatory cytokines. Interestingly, it has been reported that there is not only a cross-regulation among Thl, Th2 and Th17 effector cells but there is also a di- chotomy in the generation of Th17 and T regulatory cells. Therefore, Treg and Th17 effector cells arise in a mutually exclusive fashion, depending on whether they are activated in the presence of TGF-β or TGF-β plus inflammatory cytokines such as IL-6. This review will address the discovery of the Th17 cells, and recent progress on their development and regulation.

Evaluation of Immunomodulatory Activity of the Herbals Formula Viranur, Turmeric （Curcuma heyneana Val.） and Phyllanthus （Phyllanthus niruri L.） in Layer Chicken Vaccinated with Avian Influenza

The aim of this research was to know the effect of herbal as immunomodulator on chicken layer vaccinated with avian influenza. A total of 60 chickens were alloted into three treatment groups： control group （KA）, group KB and group KC, with 20 chicken each group. All the chickens were vaccinated with Newcastle disease （ND） in the age of one week, and a week later they were vaccinated with avian influenza （AI）. The chickens in group KB were drunken with herbal solution containing of 5 g turmeric （Curcuma heyneana Val.） and 25 g phyllanthus （Phyllanthus niruri L.） and group KC were drunken with herbal solution containing of 36 g the herbals formula Viranur and 25 g phyllanthus （Phyllanthus niruri L.）, respectively for four weeks. Thirty days after AI vaccinated, all of chicken were weighed and necropsied. Samples from bursa of Fabricius, tymus and spleen were taken for weighing and histopathological examination. The weight indexs of bursa of Fabricius, tymus and spleen were not significantly different between control group and treatment group in the considered statistically significance （P 〉 0.05）, but the treatment groups （KB and KC） had higher weight index. The histopathologically changes of spleen in both control group and treatment groups were not different, although in the group KC, in bursa of Fabricius, there was lymphocyte increase in its lymphoid follicles; and in the group KB and KC, the tymus were more widening in the cortex than medulla. The conclusion of this study showed that the herbals can stimulate lymphocyte activity.

Mechanism of Immune Hyporesponsiveness Induced by Recipientderived Immature Dendritic Cells in Rat Liver Transplantation

Objective： The use of donor-derived immature dendritic cells （imDC） has become a promising approach to induce immune tolerance or immune hyporesponsiveness. However, donor-derived imDC needs to be harvested for a few days and transfused into the recipient in 5-10 days before transplantation, which is practically impossible in a clinical setting where donor organs are mainly harvested from cadavers. Moreover, donor-derived imDC might be cleared by allogeneic reaction offsetting induced immune tolerance or immune hyporesponsiveness. In our study, we further explored the underlying mechanism of immune hyporesponsiveness induced by donor-antigen-unloaded recipient-derived imDC by transfusing these imDC into rats in 1 day before liver transplantation. This paper is to study the mechanism of immune hyporesponsiveness induced by donor-antigen-unloaded recipient-derived imDC and its protection of liver grafts in rats. Methods： 40 SD rats （donor） and 40 male Wistar rats （recipient） were randomly divided into 4 groups： control, cyclosporine A （CsA）, mature DC （mDC）, and imDC; with 10 SD rats and 10 Wistar rats for each group. Animal models of acute graft rejection were established with these rats. Corresponding treatments were given before or after transplantation. In the control group, Wistar rats received no treatment other than liver transplantation. In the CsA group, Wistar rats underwent liver transplantation plus CsA treatment （10 mg/kg·d） in the starting day 2 after transplantation. For the mDC group, recipient-derived mDC （1 × 10^6/rat） were infused intravenously via the dorsal vein of the penis to recipient rats. For the imDC group, imDC （1× 10^6/rat） were injected into recipient rats via the dorsal vein of the penis. In each group, 5 recipients were executed at 10 days after transplantation; the remaining five recipients were kept for the observation of survival time. Blood samples were collected for the measurement of ALT and TBIL; IL-2, IFN-γ, IL-4 and IL-10 and levels were measured with double-antibody sandwich ELISA. Liver tissue was harvested for HE staining and the observation of histological features. Acute rejection was evaluated with Banff classification. Expression levels of Fas-L/Fas in the grafts were detected by iminunohistochemieal staining; and western blot was used to detect the expression level of Scurfin. Results： The median survival times （MST） of the liver allografls in the CsA and imDC group were significantly longer than those in the control or mDC group （P〈0.05）. The serum levels of ALT and TBIL in the control and mDC groups were significantly higher than those of the CsA or imDC group （P〈0.05）. Compared with the CsA anti imDC group, the levels of IL-2 and IFN-γ were higher but the levels of IL-4 and IL-10 were lower than those of the control and mDC groups （P〈0.01）. Slight or no rejection reaction was found in the CsA anti imDC groups （P〈0.05）. The expression level of Scurfin protein in CD4^＋ CD25^＋ T cells of the imDC group was significantly higher than that of three other groups （P〈 0.05）. Conclusion： Donor-antigen-unloaded recipient- derived imDC is an effective treatment in inducing immune hyporesponsiveness by blocking indirect recognition in rat liver transplantation model. Survival span was significantly prolonged by its protective effect. The mechanism of immune hyporesponsiveness induced hy imDC transfusion may involve the preprocesses of T cell apoptosis induction, immune tolerance or hyporesponsiveness in T cells, induction of the shift in TH1/TH2 balance, selection activation of Th2 subset, or induction of regulatory T cell.

Immunomodulatory effect of a formula developed from American ginseng and Chinese jujube extracts in mice

Background： American ginseng（Panax quinquefolius L.） and Chinese jujube（Zizyphus jujuba Mill.） are commonly used in traditional Chinese medicine to enhance immune function. Objective： The present study aimed to develop one Chinese prescription, Shenzao Cha（SZC）, consisting of American ginseng and Chinese jujube, and systematically investigate its immunomodulation in healthy ICR mice. Methods： Normal ICR mice received intragastric administration of SZC（1.3, 2.6, and 5.2 g raw material/kg body weight） once daily for four weeks, while a control group received the same amount of sterile water. Results： SZC significantly increased the spleen and thymus indices and T-lymphocyte proliferation, while the T-lymphocyte proliferation in the 5.2 g/kg group was 1.4-fold higher than that in the control. Further, 1.3 g/kg SZC could markedly improve hemolytic activity by 25.2%, and 2.6 g/kg SZC increased the NK cell activity by 78.6% relative to the control. In addition, the activities of antioxidant enzymes（superoxide dismutase, catalase, and glutathione peroxidase）, that participated in modulating oxidative stress, were significantly increased in the liver, spleen, thymus, and serum, while the contents of malondialdehyde were dramatically decreased. Conclusions： SZC exhibited potent immunomodulatory effects on innate and adaptive immunity in healthy ICR mice, as well as potential antioxidant activity for prevention of oxidative stress, which was suggested to partly contribute to the immune enhancement.

Purification and characterization of a novel immunomodulatory protein from the medicinal mushroom Trametes versicolor

Bioactive proteins represent an important group of functional agents in medicinal mushrooms.Trametes versicolor(L.) Lloyd is a mushroom frequently used in traditional Chinese medicine for its anti-tumor and immunomodulatory activities.A new immunomodulatory protein from T.versicolor,named TVC,was purified by ammonium sulfate precipitation,ion-exchange chromatography and gel filtration chromatography.Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the purified protein revealed a single band with a molecular weight of 15.0 kD.Native polyacrylamide gel analysis revealed a band at 30 kD,indicating that TVC exists in solution as a homodimer.Isoelectric focusing showed that TVC was an acidic protein with an isoelectric point of 4.0.TVC was found to lack carbohydrate modifications(based on periodic acid/Schiff staining) and it does not agglutinate mouse red blood cells,suggesting that TVC is not a lectin-like protein.Biological activity assays dem-onstrated that TVC can enhance the proliferation of splenocytes,while it has no stimulatory effects on CD4+and CD8+T cells. TVC markedly increases the proliferation of human peripheral blood lymphocytes in a dose-dependent manner and enhances the production of both nitric oxide and tumor necrosis factor-alpha by lipopolysaccharide-induced murine macrophages.The results indicate that TVC is an immunostimulant that can boost immune response.Comparison of the N-terminal amino acid residues and mass spectrometry results with the protein database revealed no homologous proteins.

Isolation, chemical characterization, and immunomodulatory activity of naturally acetylated hemicelluloses from bamboo shavings

Bamboo shavings, the outer or intermediate layer of bamboo stems, are the bulk of by-products produced in bamboo processing. In this study we investigated the isolation, chemical characterization, and immunostimulatory activity in vitro of the hemicelluloses from bamboo shavings. Shavings were first pretreated by steam explosion. The optimal pretreatment was found to be steam explosion at 2.2 MPa for 1 min. Following this pretreatment, the yield of hemicelluloses reached（2.05±0.22）%（based on the dry dewaxed raw materials）, which was 5.7-fold higher than that of untreated samples. Bamboo-shavings hemicellulose（BSH） was then prepared by hot water extraction and ethanol precipitation from the steam-exploded shavings. Purification of BSH by anion-exchange chromatography of diethylaminoethanol（DEAE）-sepharose Fast Flow resulted in a neutral fraction（BSH-1, purity of 95.3%, yield of 1.06%） and an acidic fraction（BSH-2, purity of 92.5%, yield of 0.79%）. The weight-average molecular weights（Mw） of BSH-1 and BSH-2 were 12 800 and 11 300 g/mol, respectively. Chemical and structural analyses by Fourier transform infrared spectroscopy（FT-IR）, 1D（^1H and ^13C） and 2D（heteronuclear single quantum correlation（HSQC）） nuclear magnetic resonance（NMR） spectra revealed that BSH-1 was O-acetylated-arabinoxylan and BSH-2 was O-acetylated-（4-Omethylglucurono）-arabinoxylan. BSH-1 had a higher content of acetyl groups than BSH-2. For the immunomodulatory activity in vitro, BSH and BSH-2 significantly stimulated mouse splenocyte proliferation while BSH-1 had no effect; BSH, BSH-1, and BSH-2 markedly enhanced the phagocytosis activity and nitric oxide production of the murine macrophage RAW264.7 in a dose-dependent manner. Our results suggest that the water-extractable hemicelluloses from steam-exploded bamboo shavings are naturally acetylated and have immunostimulatory activity.

Effects of Acupuncture-moxibustion on Monocyte Th1/Th2 Cytokine in Peripheral Blood of Patients with Perennial Allergic Rhinitis

Objective： To observe the effects of acupuncture-moxibustion on symptoms, signs, and Th1/Th2 cytokine, and regulation on Th1/Th2 in patients with perennial allergic rhinitis（PAR） to provide experimental basis for acupuncture treating allergic rhinitis and investigate the mechanism. Methods： Thirty patients with allergic rhinitis were treated with acupuncture-moxibustion, and 30 healthy cases were the control. Clinical symptoms, signs, and nasal mucosa were observed, and contents of IL-4, IFN-γ, and granulocyte-macrophage colony stimulating factor （GM-CSF） in the supernatant of peripheral blood monocyte cultured with PHA by ELISA, before treatment, after one course of treatment, and after two courses of treatment. Results： Before the treatment, the contents of IL-4, and GM-CSF were higher （P〈0.01） and IFN-γ was lower （P〈0.01） in the PAR cases than in the control cases. In the PAR cases, the content of GM-CSF was positive correlation with that of IL-4 （P〈0.01）, and negative correlation with IFN-7 （P〈0.01）. After the treatment, contents of IL-4 and GM-CSF were lowed （P〈0.01）, content of IFN-γ was increased （P〈0.05）, and all IL-4, GM-CSF and IFN-γ had no difference compared with those in the control cases. Conclusion： Acupuncture- moxibustion could improve the symptoms and signs in PAR patients, enhance the immune function. It may be achieved by regulating the expression of Th1 and Th2, correcting the imbalance of Th1/Th2.

Antioxidant and immunomodulatory activities of a polysaccharide from Flammulina velutipes

OBJECTIVE: To evaluate the antioxidant and immunomodulatory activities of a unique polysaccharide from the medicinal fungus Flammulina velutipes in vitro.METHODS: Using water extraction and alcohol precipitation, crude polysaccharides were obtained. After purification by DEAE-cellulose 52 ion exchange chromatography and Sephacryl S-300 HR gel filtration chromatography, High performance liquid chromatography equipped with evaporative light-scattering detector, Infrared radiation and Nuclear magnetic resonance were used to evaluate the structure of the polysaccharide. Its immunomodulatory activity was measured by examining the production of nitric oxide(NO) and cytokine secretion, and via lymphocyte proliferation experiments. Its effects on the scavenging activities of hydroxyl radical, superoxide anion and reducing power were also measured.RESULTS: A water-soluble polysaccharide, Flammulina velutipes polysaccharide I-A(FVP I-A), was obtained with a molecular mass of 8.14×104Da determined by high performance gel permeation chromatography. An in vitro antioxidant assay indicated that FVP I-A could scavenge hydroxyl radical, superoxide anion and possessed reducing power and could largely promote NO production and augment the interleukin-1β, interleukin-6, and tumor necrosis factor-α secretion by RAW264.7 macrophages(P<0.05). Moreover, FVP I-A could promote lymphocyte proliferation(P<0.05), and synergistically enhance the augmentation of the proliferation of mouse lymphocytes by concanavalin A and lipopolysaccharides(P<0.01, P<0.05).CONCLUSION: The FVP I-A obtained from Flammulina velutipes possessed antioxidant activity and could enhance non-specific and specific immune responses in vitro.

Medullary thymic epithelial cells,the indispensable player in central tolerance

Crosstalk between thymocytes and thymic epithelial cells is critical for T cell development and the establishment of central tolerance.Medullary thymic epithelial cells(mTECs) play important roles in the late stage of T cell development,especially negative selection and Treg generation.The function of mTECs is highly dependent on their characteristic features such as ectopic expression of peripheral tissue restricted antigens(TRAs) and their master regulator-autoimmune regulator(Aire),expression of various chemokines and cytokines.In this review,we summarize the current understanding of cellular and molecular mechanisms of mTEC development and its functions in T cell development and the establishment of central tolerance.The open questions in this field are also discussed.Understanding the function and underlying mechanisms of mTECs will contribute to the better control of autoimmune diseases and the improvement of immune reconstitution during aging or after infection,chemotherapy or radiotherapy.

Development of artemisinin drugs in the treatment of autoimmune diseases

Artemisinin drugs are a family of sesquiterpene trioxane lactone agents originally derived from Artemisia annua L. Due to the big victory in the antimalarial battle,the 2015 Nobel Prize goes to the discoverer of artemisininbased therapy for malaria. Beyond antimalaria, artemisinin and its derivatives are also being investigated in diseases like schistosomiasis, viral infection, cancers and inflammation. Over the past decades, the anti-inflammatory and immunomodulatory effects of artemisinin drugs have been comprehensively studied. In this article, we will briefly describe the development of artemisinin drugs, especially novel artemisinin derivatives, in the treatment of autoimmune diseases.

Total body irradiation of donors can alter the course of tolerance and induce acute rejection in a spontaneous tolerance rat liver transplantation model

Liver transplantation is an established therapy for end-stage liver diseases. Graft rejection occurs unless the recipient receives immunosuppression after transplantation. This study aimed to explore the mechanism of acute rejection of liver allografts in rats pre-treated with total body irradiation to eliminate passenger lymphocytes and to define the role of CD4＋CD25＋ regulatory T cells in the induction of immunotolerance in the recipient. Male Lewis rats were used as donors and male DA rats were re- cipients. Rats were randomly assigned to the following four groups： control group, homogeneity liver transplantation group, idio-immunotolerance group and acute rejection group. After transplantation, the survival time of each group, serum alanine aminotransferase, total bilirubin levels, number of Foxp3＋CD4＋CD25＋ regulatory T cells, expression of glucocorticoid-induced tumor necrosis factor receptor on T cell subgroups, histopathology of the hepatic graft and spleen cytotoxic T lymphocyte lytic activity were measured. In the acute rejection group, where donors were preconditioned with total body in＇adiation before liver transplantation, all recipients died between day 17 and day 21. On day 14, serum alanine aminotransferase increased signifi- cantly to （459.2±76.9） U L^- 1, total bilirubin increased to （124.1±33.7） μmol L-1 （P〈0.05） and the ratio of Foxp3＋CD4＋CD25＋ regulatory T cells decreased significantly to 1.50%±0.50% （P〈0.05） compared with the other groups. Analysis of the T cell subpopulations in the acute rejection group varied from the other groups. Histological analysis showed typical changes of acute rejection in the acute rejection group only. Preconditioning of the donors with total body irradiation eliminated passenger lymphocytes of the liver graft, and thus affected the course of tolerance and induced acute rejection after liver transplantation.