[Objectives]This study aimed to observe the effects of different processed products of Radix Codonopsis on intestinal flora in rats with spleen deficiency.[Methods]Rat models with spleen deficiency were established by...[Objectives]This study aimed to observe the effects of different processed products of Radix Codonopsis on intestinal flora in rats with spleen deficiency.[Methods]Rat models with spleen deficiency were established by bitter-cold purgation method with Radix et Rhizoma Rhei.Normal group,model group,Radix Codonopsis group,fried Radix Codonopsis group,rice-fried Radix Codonopsis group,honey-fried Radix Codonopsis group and bran-fired Radix Codonopsis group were designed.After subjecting to corresponding treatments,the changes in the quantity of intestinal microorganisms of the rats were detected.[Results]There was no significant change in the quantity of intestinal microorganisms of the rats in the normal group and model group.The rats in the rice-fried Radix Codonopsis group were administered after successful modeling,and the abundance of Bifidobacterium and Lactobacillus in the intestines of the rats increased,and the quantity of Escherichia coli and Staphylococci reduced.The rats in the Radix Codonopsis group,fried Radix Codonopsis groups,honey-fried Radix Codonopsis group and bran-fried Radix Codonopsis group were administered after successful modeling,and the abundance of Bifidobacterium and Lactobacillus in the intestines of the rats increased(the increases were smaller than those in the rice-fried Radix Codonopsis group),and the abundance of E.coli and Staphylococci reduced,close to normal levels.[Conclusions]Different processed products of Radix Codonopsis have obvious regulation effect on intestinal flora of rats with spleen deficiency,and the regulation effect of rice-fried Radix Codonopsis on rats with spleen deficiency is better than that of Radix Codonopsis,fried Radix Codonopsis,honey-fried Radix Codonopsis and bran-fried Radix Codonopsis.展开更多
T-cell subsets from peripheral blood and spleen were investigated prospectively by flow cytometry in a murine intrahepatic implanted tumor model. Peripheral blood OX-19+ cells (pan T-cells) and W3/25+ cells (Th cells)...T-cell subsets from peripheral blood and spleen were investigated prospectively by flow cytometry in a murine intrahepatic implanted tumor model. Peripheral blood OX-19+ cells (pan T-cells) and W3/25+ cells (Th cells) decreased with tumor development in tumor-bearing rats, giving significant differences when compared with healthy rats. No significant changes were found in OX-8+ cells (Ts cells). Hence, Th Ts ratio in tumor-bearing rats was lower than that in control group. Meanwhile, on day 17 following tumor implantation, in tumor-bearing rats with intrahepatic or peritoneal metastasis, there were less W3/25+ cells and more OX-8+ cells than those of hepatoma-bearing rats without metastasis (p<0.01). In the spleen, the phenotypes of lymphocyte markers showed less OX-8+ cells and more OX-12+ cells (B cells) tumor-bearing rats. It was suggested that, in tumor-bearing host, not only was T-cell immune function inhibited, but also there was abnormal distribution of T-cell subsets. It seems that there is a close relationship between tumor growth and its spread and a lower Th/Ts ratio.展开更多
Salmonella typhi is a facultative intracellular pathogen that causes typhoid fever in humans. In the present study, the effect of Salmonella typhi infection on hematological indices and spleen histology in Wistar rats...Salmonella typhi is a facultative intracellular pathogen that causes typhoid fever in humans. In the present study, the effect of Salmonella typhi infection on hematological indices and spleen histology in Wistar rats was investigated and was followed by an evaluation of the ameliorative potential of the methanol leaf extract of Chromolaena odorata (MLECO) compared with ciprofloxacin treatment. The animals were divided into six groups: group 1 was normal control, group 2 was infected with Salmonella typhi without treatment (negative control), groups 3, 4 and 5 were Salmonella typhi infected and treated with 100 mg/kg, 200 mg/kg and 400 mg/kg of the extract respectively and group 6 was also Salmonella typhi infected and treated with 500 mg/70kg of ciprofloxacin. The animals were inoculated with a single infectious dose of Salmonella typhi bacteria and thereafter, treated with the extract and ciprofloxacin for a period of seventeen days, after the animals were confirmed infected. The rats were humanely sacrificed and blood samples taken for haematological investigations, and the spleen harvested and processed for histological examinations. Chromolaena odorata administration reversed the adverse hematotoxicity and histopathological changes in the spleen induced by?Salmonella typhi?infection.展开更多
[Objectives] To establish animal models of fatty liver due to liver depression and spleen deficiency that were suitable for activity discovery of traditional Chinese medicine( TCM) compounds,efficacy evaluation,new dr...[Objectives] To establish animal models of fatty liver due to liver depression and spleen deficiency that were suitable for activity discovery of traditional Chinese medicine( TCM) compounds,efficacy evaluation,new drug research and development and correspondence between prescription and syndrome of TCM. [Methods] A syndrome score scale that was suitable for evaluating the rat models was established according to the evolvement rules of etiology and pathogenesis of TCM and the modern clinical pathological mechanism. At the same time,bifendate pills and Sanqi Zhigan pills were selected as drug counterevidence for the models. Rats in model groups were given different proportions of high-fat and low-protein fodder and different concentrations of alcohol every day,and intraperitoneally injected with porcine serum twice a week. Drug groups were given with bifendate pills and Sanqi Zhigan pills( 8. 1 mg/kg,and 2. 7 g/kg) respectively for 14 consecutive days.During the experiment,general status,weight,daily fodder intake and daily water intake of the animals were observed,and TCM syndromes were scored. After the experiment,the levels of alanine aminotransferase( ALT),aspartate aminotransferase( AST),γ-glutamine transpeptidase( γ-GT),total cholesterol( TC),triglycerides( TG),low density lipoprotein-cholesterol( LDL-C),and high density lipoprotein-cholesterol( HDL-C) in serum were detected,and the pathological changes in liver tissue were observed. [Results] Compared with the control group,body weight,daily fodder and water intake of rats increased slowly in the model group,and the levels of ALT,AST,γ-GT,TC,TG and LDL-C increased significantly,while the level of HDL-C dropped. Pathological examination showed that steatosis and fat granule were observed in hepatocytes of rats in the model group. Behavioral observation found that main symptoms and minor symptoms of rats in the model group conformed to the syndrome manifestation of liver depression and spleen deficiency,which suggested that the three model groups were established successfully. Among them,three rats died in model group 1,and one rat died in model group 2. The manifestation of all the above lesions can be alleviated by drug counterevidence. [Conclusions]The animal model of fatty liver due to liver depression and spleen deficiency shows an obviously lower mortality and shorter duration and can be used for research of correlation between prescription and syndrome and its mechanism.展开更多
目的观察黄芪建中汤对脾胃虚寒证胃溃疡大鼠炎症因子及HGF/c-Met信号通路的影响。方法将60只大鼠随机分为4组,即正常组、模型组、黄芪建中汤组[黄芪建中汤6.8 g/(kg·d)]、奥美拉唑组[奥美拉唑肠溶胶囊4.2 mg/(kg·d)],每组15...目的观察黄芪建中汤对脾胃虚寒证胃溃疡大鼠炎症因子及HGF/c-Met信号通路的影响。方法将60只大鼠随机分为4组,即正常组、模型组、黄芪建中汤组[黄芪建中汤6.8 g/(kg·d)]、奥美拉唑组[奥美拉唑肠溶胶囊4.2 mg/(kg·d)],每组15只大鼠。正常组除外,其他组采用耗气破气法结合饥饱失常法进行大鼠脾胃虚寒证模型造模,再采用冰醋酸法建立大鼠胃溃疡模型。比较各组大鼠体质量、溃疡指数;HE染色观察大鼠胃组织病理学变化;采用酶联免疫吸附法检测血清中白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)含量;免疫组化法检测胃组织中肝细胞生长因子(HGF)、肝细胞生长因子受体(c-Met)表达;荧光定量PCR检测胃组织HGF、c-Met m RNA水平。结果与正常组相比,模型组大鼠体质量降低,溃疡指数升高,IL-6、IL-1β、TNF-α含量升高,HGF升高,HGF、c-Met m RNA升高(P<0.05);与模型组相比,黄芪建中汤组和奥美拉唑组大鼠体质量升高,溃疡指数降低,IL-6、IL-1β、TNF-α降低,HGF升高,HGF、c-Met mRNA升高(P<0.05)。结论黄芪建中汤可以通过抑制炎症因子、调节HGF/c-Met通路的表达促进胃黏膜修复。展开更多
Dimethyl curcumin,a synthetic derivative of curcumin,has good anti-cancer,anti-arthritis and anti-inflammatory properties,but underline mechanism was unclear.Activation,differentiation,proliferation and apoptosis of l...Dimethyl curcumin,a synthetic derivative of curcumin,has good anti-cancer,anti-arthritis and anti-inflammatory properties,but underline mechanism was unclear.Activation,differentiation,proliferation and apoptosis of lymphocytes have important functions during arthritis development and immune homeostasis.Over-activation of lymphocyte causes inflammatory cytokines storm,leading to an immune imbalance and tissue damages.The aim of this study was to investigate the anti-inflammation mechanism of liposome encapsulated dimethyl curcumin(Lipo-DiMC)on over-activated rat spleen lymphocytes.In this study,Lipo-DiMC was produced to increase the solubility;the primary rat spleen lymphocytes were extracted and the Concanavalin A induced cell activation model was established to study the cellular responses to Lipo-DiMC treatment in-vitro.The results showed that Lipo-DiMC suppressed Concanavalin A-induced cell proliferation,inhibited cells entering G2/M phase,and reduced the ratio of necrosis/apoptosis by manipulating intracellular p53/p21/PCNA/JNK-1 pathways.Furthermore,Lipo-DiMC increased the accumulations of intracellular matrix metalloproteinase-9 and reduced matrix metalloproteinase-9 secretion of rat spleen lymphocytes.Also,Lipo-DiMC increased intracellular caspase-3 expression and reduced Cat-C activity in activated rat spleen lymphocytes,involving in intracellular proteolysis.Our findings suggest that dimethyl curcumin effectively alleviates Concanavalin A induced over-activation of rat spleen lymphocytes,thereby inhibiting inflammatory cytokines storm and restoring cell homeostasis.展开更多
A previous study from our group showed that Jiawei Wendan decoction inhibits protein expression of interleukin-1β, 2, and 6, as well as plasma neuropeptide Y, P substance and somatostatin in the hippocampus of depres...A previous study from our group showed that Jiawei Wendan decoction inhibits protein expression of interleukin-1β, 2, and 6, as well as plasma neuropeptide Y, P substance and somatostatin in the hippocampus of depression rat models. The present study analyzed the influence of Jiawei Wendan decoction on the mitogen-activated protein kinase signal transduction pathway in the hippocampus. Results demonstrated that Jiawei Wendan decoction effectively upregulated expression of small molecular G proteins, extracellular regulated kinase 1/2, and activated ribosomal S6 kinase protein in the rat hippocampus. In addition, Jiawei Wendan decoction exhibits antidepressant effects similar to fluoxetine. The underlying mechanisms were shown to be dependent on increased mitogen-activated protein kinase signal transduction pathway activity.展开更多
BACKGROUND: The effect of pituitary adenylate cyclase activating polypeptide (PACAP) during traumatic brain injury (TBI) and whether it can modulate secondary injury has not been reported previously. The present ...BACKGROUND: The effect of pituitary adenylate cyclase activating polypeptide (PACAP) during traumatic brain injury (TBI) and whether it can modulate secondary injury has not been reported previously. The present study evaluated the potential protective effects of ventricular infusion of PACAP in a rat model of TBI.METHODS: Male Sprague Dawley rats were randomly divided into 3 treatment groups (n=6, each): sham-operated, vehicle (normal saline)+TBI, and PACAP+TBI. Normal saline or PACAP (1 μg/5 μL) was administered intracerebroventricularly 20 minutes before TBI. Right parietal cortical contusion was produced via a weight-dropping method. Brains were extracted 24 hours after trauma. Histological changes in brains were examined by HE staining. The numbers of CD4+ and CD8+ T cells in blood and the spleen were detected via flow cytometry.RESULTS: In injured brain regions, edema, hemorrhage, inflammatory cell infiltration, and swollen and degenerated neurons were observed under a light microscope, and the neurons were disorderly arrayed in the hippocampi. Compared to the sham group, average CD4+ CD8+ lymphocyte counts in blood and the spleen were significantly decreased in rats that received TBl+vehicle, and CD4- CD8+ were increased. In rats administered PACAP prior to TBI, damage was attenuated as evidenced by significantly increased CD4+, and decreased CD8+, T lymphocytes in blood and the spleen.CONCLUSION: Pretreatment with PACAP may protect against TBI by influencing periphery T cellular immune function.展开更多
基金Supported by National Natural Science Foundation of China(No.81360524)Youth Foundation of Guangxi University of Chinese Medicine(No.2019QN036)+2 种基金Basic Ability Improvement Project for Scientific Research of Young and Middle-aged Teachers in Colleges and Universities of Guangxi(No.2019KY0341)Key Research and Development Project of Science and Technology Department of Guangxi(No.AB19110003)Third-class Chinese(Zhuang)Medicine Chemistry and Quality Analysis Laboratory of National Administration of Traditional Chinese Medicine(Guo Zhong Yi Yao Fa 2009[21]).
文摘[Objectives]This study aimed to observe the effects of different processed products of Radix Codonopsis on intestinal flora in rats with spleen deficiency.[Methods]Rat models with spleen deficiency were established by bitter-cold purgation method with Radix et Rhizoma Rhei.Normal group,model group,Radix Codonopsis group,fried Radix Codonopsis group,rice-fried Radix Codonopsis group,honey-fried Radix Codonopsis group and bran-fired Radix Codonopsis group were designed.After subjecting to corresponding treatments,the changes in the quantity of intestinal microorganisms of the rats were detected.[Results]There was no significant change in the quantity of intestinal microorganisms of the rats in the normal group and model group.The rats in the rice-fried Radix Codonopsis group were administered after successful modeling,and the abundance of Bifidobacterium and Lactobacillus in the intestines of the rats increased,and the quantity of Escherichia coli and Staphylococci reduced.The rats in the Radix Codonopsis group,fried Radix Codonopsis groups,honey-fried Radix Codonopsis group and bran-fried Radix Codonopsis group were administered after successful modeling,and the abundance of Bifidobacterium and Lactobacillus in the intestines of the rats increased(the increases were smaller than those in the rice-fried Radix Codonopsis group),and the abundance of E.coli and Staphylococci reduced,close to normal levels.[Conclusions]Different processed products of Radix Codonopsis have obvious regulation effect on intestinal flora of rats with spleen deficiency,and the regulation effect of rice-fried Radix Codonopsis on rats with spleen deficiency is better than that of Radix Codonopsis,fried Radix Codonopsis,honey-fried Radix Codonopsis and bran-fried Radix Codonopsis.
文摘T-cell subsets from peripheral blood and spleen were investigated prospectively by flow cytometry in a murine intrahepatic implanted tumor model. Peripheral blood OX-19+ cells (pan T-cells) and W3/25+ cells (Th cells) decreased with tumor development in tumor-bearing rats, giving significant differences when compared with healthy rats. No significant changes were found in OX-8+ cells (Ts cells). Hence, Th Ts ratio in tumor-bearing rats was lower than that in control group. Meanwhile, on day 17 following tumor implantation, in tumor-bearing rats with intrahepatic or peritoneal metastasis, there were less W3/25+ cells and more OX-8+ cells than those of hepatoma-bearing rats without metastasis (p<0.01). In the spleen, the phenotypes of lymphocyte markers showed less OX-8+ cells and more OX-12+ cells (B cells) tumor-bearing rats. It was suggested that, in tumor-bearing host, not only was T-cell immune function inhibited, but also there was abnormal distribution of T-cell subsets. It seems that there is a close relationship between tumor growth and its spread and a lower Th/Ts ratio.
文摘Salmonella typhi is a facultative intracellular pathogen that causes typhoid fever in humans. In the present study, the effect of Salmonella typhi infection on hematological indices and spleen histology in Wistar rats was investigated and was followed by an evaluation of the ameliorative potential of the methanol leaf extract of Chromolaena odorata (MLECO) compared with ciprofloxacin treatment. The animals were divided into six groups: group 1 was normal control, group 2 was infected with Salmonella typhi without treatment (negative control), groups 3, 4 and 5 were Salmonella typhi infected and treated with 100 mg/kg, 200 mg/kg and 400 mg/kg of the extract respectively and group 6 was also Salmonella typhi infected and treated with 500 mg/70kg of ciprofloxacin. The animals were inoculated with a single infectious dose of Salmonella typhi bacteria and thereafter, treated with the extract and ciprofloxacin for a period of seventeen days, after the animals were confirmed infected. The rats were humanely sacrificed and blood samples taken for haematological investigations, and the spleen harvested and processed for histological examinations. Chromolaena odorata administration reversed the adverse hematotoxicity and histopathological changes in the spleen induced by?Salmonella typhi?infection.
基金Supported by National Major Scientific and Technological Special Project for"Significant New Drugs Development"(2009ZX09502-015)Autonomous Innovation and Achievement Transformation Project of Shandong Province(2014ZZCX02104)+1 种基金Project of National Natural Science Foundation(81374059)Special Fund for Taishan Scholar Project(Ns201511107)
文摘[Objectives] To establish animal models of fatty liver due to liver depression and spleen deficiency that were suitable for activity discovery of traditional Chinese medicine( TCM) compounds,efficacy evaluation,new drug research and development and correspondence between prescription and syndrome of TCM. [Methods] A syndrome score scale that was suitable for evaluating the rat models was established according to the evolvement rules of etiology and pathogenesis of TCM and the modern clinical pathological mechanism. At the same time,bifendate pills and Sanqi Zhigan pills were selected as drug counterevidence for the models. Rats in model groups were given different proportions of high-fat and low-protein fodder and different concentrations of alcohol every day,and intraperitoneally injected with porcine serum twice a week. Drug groups were given with bifendate pills and Sanqi Zhigan pills( 8. 1 mg/kg,and 2. 7 g/kg) respectively for 14 consecutive days.During the experiment,general status,weight,daily fodder intake and daily water intake of the animals were observed,and TCM syndromes were scored. After the experiment,the levels of alanine aminotransferase( ALT),aspartate aminotransferase( AST),γ-glutamine transpeptidase( γ-GT),total cholesterol( TC),triglycerides( TG),low density lipoprotein-cholesterol( LDL-C),and high density lipoprotein-cholesterol( HDL-C) in serum were detected,and the pathological changes in liver tissue were observed. [Results] Compared with the control group,body weight,daily fodder and water intake of rats increased slowly in the model group,and the levels of ALT,AST,γ-GT,TC,TG and LDL-C increased significantly,while the level of HDL-C dropped. Pathological examination showed that steatosis and fat granule were observed in hepatocytes of rats in the model group. Behavioral observation found that main symptoms and minor symptoms of rats in the model group conformed to the syndrome manifestation of liver depression and spleen deficiency,which suggested that the three model groups were established successfully. Among them,three rats died in model group 1,and one rat died in model group 2. The manifestation of all the above lesions can be alleviated by drug counterevidence. [Conclusions]The animal model of fatty liver due to liver depression and spleen deficiency shows an obviously lower mortality and shorter duration and can be used for research of correlation between prescription and syndrome and its mechanism.
文摘目的观察黄芪建中汤对脾胃虚寒证胃溃疡大鼠炎症因子及HGF/c-Met信号通路的影响。方法将60只大鼠随机分为4组,即正常组、模型组、黄芪建中汤组[黄芪建中汤6.8 g/(kg·d)]、奥美拉唑组[奥美拉唑肠溶胶囊4.2 mg/(kg·d)],每组15只大鼠。正常组除外,其他组采用耗气破气法结合饥饱失常法进行大鼠脾胃虚寒证模型造模,再采用冰醋酸法建立大鼠胃溃疡模型。比较各组大鼠体质量、溃疡指数;HE染色观察大鼠胃组织病理学变化;采用酶联免疫吸附法检测血清中白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)含量;免疫组化法检测胃组织中肝细胞生长因子(HGF)、肝细胞生长因子受体(c-Met)表达;荧光定量PCR检测胃组织HGF、c-Met m RNA水平。结果与正常组相比,模型组大鼠体质量降低,溃疡指数升高,IL-6、IL-1β、TNF-α含量升高,HGF升高,HGF、c-Met m RNA升高(P<0.05);与模型组相比,黄芪建中汤组和奥美拉唑组大鼠体质量升高,溃疡指数降低,IL-6、IL-1β、TNF-α降低,HGF升高,HGF、c-Met mRNA升高(P<0.05)。结论黄芪建中汤可以通过抑制炎症因子、调节HGF/c-Met通路的表达促进胃黏膜修复。
基金This work is supported by the Start-up Research Laboratory for Over-sea Talent Fund,China(No.Z391405)to ProfXiaoying Zhou and the Changzhou University Undergraduate Innovation and Entrepreneurship Fund,China(No.2019-02-C-96)to Ya-Ming Guo.
文摘Dimethyl curcumin,a synthetic derivative of curcumin,has good anti-cancer,anti-arthritis and anti-inflammatory properties,but underline mechanism was unclear.Activation,differentiation,proliferation and apoptosis of lymphocytes have important functions during arthritis development and immune homeostasis.Over-activation of lymphocyte causes inflammatory cytokines storm,leading to an immune imbalance and tissue damages.The aim of this study was to investigate the anti-inflammation mechanism of liposome encapsulated dimethyl curcumin(Lipo-DiMC)on over-activated rat spleen lymphocytes.In this study,Lipo-DiMC was produced to increase the solubility;the primary rat spleen lymphocytes were extracted and the Concanavalin A induced cell activation model was established to study the cellular responses to Lipo-DiMC treatment in-vitro.The results showed that Lipo-DiMC suppressed Concanavalin A-induced cell proliferation,inhibited cells entering G2/M phase,and reduced the ratio of necrosis/apoptosis by manipulating intracellular p53/p21/PCNA/JNK-1 pathways.Furthermore,Lipo-DiMC increased the accumulations of intracellular matrix metalloproteinase-9 and reduced matrix metalloproteinase-9 secretion of rat spleen lymphocytes.Also,Lipo-DiMC increased intracellular caspase-3 expression and reduced Cat-C activity in activated rat spleen lymphocytes,involving in intracellular proteolysis.Our findings suggest that dimethyl curcumin effectively alleviates Concanavalin A induced over-activation of rat spleen lymphocytes,thereby inhibiting inflammatory cytokines storm and restoring cell homeostasis.
基金the National Natural Science Foundation of China, No. 30973732
文摘A previous study from our group showed that Jiawei Wendan decoction inhibits protein expression of interleukin-1β, 2, and 6, as well as plasma neuropeptide Y, P substance and somatostatin in the hippocampus of depression rat models. The present study analyzed the influence of Jiawei Wendan decoction on the mitogen-activated protein kinase signal transduction pathway in the hippocampus. Results demonstrated that Jiawei Wendan decoction effectively upregulated expression of small molecular G proteins, extracellular regulated kinase 1/2, and activated ribosomal S6 kinase protein in the rat hippocampus. In addition, Jiawei Wendan decoction exhibits antidepressant effects similar to fluoxetine. The underlying mechanisms were shown to be dependent on increased mitogen-activated protein kinase signal transduction pathway activity.
文摘BACKGROUND: The effect of pituitary adenylate cyclase activating polypeptide (PACAP) during traumatic brain injury (TBI) and whether it can modulate secondary injury has not been reported previously. The present study evaluated the potential protective effects of ventricular infusion of PACAP in a rat model of TBI.METHODS: Male Sprague Dawley rats were randomly divided into 3 treatment groups (n=6, each): sham-operated, vehicle (normal saline)+TBI, and PACAP+TBI. Normal saline or PACAP (1 μg/5 μL) was administered intracerebroventricularly 20 minutes before TBI. Right parietal cortical contusion was produced via a weight-dropping method. Brains were extracted 24 hours after trauma. Histological changes in brains were examined by HE staining. The numbers of CD4+ and CD8+ T cells in blood and the spleen were detected via flow cytometry.RESULTS: In injured brain regions, edema, hemorrhage, inflammatory cell infiltration, and swollen and degenerated neurons were observed under a light microscope, and the neurons were disorderly arrayed in the hippocampi. Compared to the sham group, average CD4+ CD8+ lymphocyte counts in blood and the spleen were significantly decreased in rats that received TBl+vehicle, and CD4- CD8+ were increased. In rats administered PACAP prior to TBI, damage was attenuated as evidenced by significantly increased CD4+, and decreased CD8+, T lymphocytes in blood and the spleen.CONCLUSION: Pretreatment with PACAP may protect against TBI by influencing periphery T cellular immune function.