Traditionally, macroautophagy (autophagy) is viewed as a pathway of cell survival. Autophagy ensures the elimination of damaged or unwanted cytosolic components and provides a source of cellular nutrients during periods of stress. Interestingly, autophagy can also directly intersect with, and impact, other major pathways of cellular function. Here, we will review the contribution of autophagy to pathways of antigen presentation. The autophagy machinery acts to modulate both MHCI and MHCII antigen presentation. As such autophagy is an important participant in pathways that elicit host cell immunity and the elimination of infectious pathogens.
Animals ; Antigen Presentation ; Autophagy ; HLA Antigens ; immunology ; Humans ; Thymus Gland ; cytology ; immunology

OBJECTIVETo study the effects of nucleotides on apoptosis of thymocytes in mice.

METHODSApoptosis model in vivo was first established and 25 KM mice, 4 weeks old, were randomly divided into 5 groups. One group was control, and the others were test groups. Mice in test groups were injected with DEX (25 mg/kg) and the controls were treated with normal saline. 4, 8, 16, and 24 hours later the thymus and spleen were weighed and lymphocytes in thymus were separated. The apoptosis of lymphocytes was analyzed by using DNA electrophoresis and flow cytometry. 16 hours later lymphocytes apoptosis reached a peak and lasted 24 hours. Methods used to establish apoptosis model in vivo were: mice (4 weeks old) were injected with DEX (25 mg/kg), and thymus lymphocytes were separated 16 hours later and analyzed. The effects of nucleotides on apoptosis of mice thymocytes were investigated in experiment 2. Sixty KM mice, 20 g +/- 2g, 4 weeks old, were divided into four treatments: negative control group (NC), positive control group (PC), nucleotides-additive group 1 (NTS1) and nucleotides-additive group 2 (NTS2).

RESULTSBody weight gained in NST1 and NST2 were 3.71 g, 4.01 g respectively, significantly higher than NC (2.74 g) (P < 0.01) and in NST2 was significantly higher than in PC (2.96 g) (P < 0.01). Thymus index and spleen index were decreased significantly (P < 0.01), and no difference was found with the supplementation of nucleotides (P > 0.05). [Ca2+]i increased to 167.37 nmol/L, 191.16 nmol/L, 180.78 nmol/L in PC, NST1 and NST2 with DEX, being significantly higher than in NC (103.76 nmol/L) (P < 0.01). The percent of apoptosised thymocytes in groups were 0.31%, 11.93%, 9.82%, 11.15%, respectively. Thymus index and spleen index, cell apoptosis and [Ca2+]i were not differed significantly among PC, NTS1 and NTS2 groups.

CONCLUSIONNucleotides should have no significant effects on apoptosis of thymocytes in mice in vivo.

Animals ; Apoptosis ; drug effects ; Dexamethasone ; pharmacology ; Lymphocytes ; cytology ; Male ; Mice ; Nucleotides ; pharmacology ; Random Allocation ; Thymus Gland ; cytology

To investigate the development of the reticular network of the thymus with aging and under pathologic conditions, we performed reticulin stains on the following samples; 5 fetal thymi (22 to 33 weeks of gestational age) and 35 postnatal thymi (less than 1 month to 33 years of age). The latter included 1 hyperplastic thymus, 4 pathologically involuted thymi and 1 physiologically involuted thymus as well as 29 normal thymi. Reticulin fibers were invariably seen along the capsule and interlobular septae of all the thymi. In fetal thymi, reticulin fibers circumscribed only cortical blood vessels and Hassall's corpuscles. Postnatal thymi from the children aged less than 1 month showed discontinuous reticulin fibers along the blood vessels of the corticomedullary junction. With aging, the amount of reticulin fibers increased and formed a "fibroreticular network(FRN)" from the branching point of the interlobular septae along the corticomedullary junction. It completely circumscribed the outer medulla in fully developed thymi. In the hyperplastic thymus, the reticular network retained its original structure. Both pathologically and physiologically involuted thymi revealed irregularly collapsed reticulin fibers. These findings suggest that the reticular network of the thymus consists of FRNs as well as capsule and interlobular septae and matures with aging before involution.
Adult ; Aging/*pathology ; Child ; Child, Preschool ; Female ; Humans ; Hyperplasia ; Infant ; Infant, Newborn ; Pregnancy ; Thymus Gland/cytology/*pathology

The nomenclature "embryonic lymphoid tissue inducer (LTi) cell" reflects the fundamental role of the cell in secondary lymphoid tissue organization. In addition, it is equally important in primary lymphoid tissue development as it regulates central tolerance to self-antigens in the thymus. An adult LTi cell constitutively expresses two sets of tumor necrosis factor (TNF) family members, whereas its embryonic counterpart expresses only one. The first set is lymphotoxin (LT)alpha, LTbeta, and TNFalpha, which are essential for the secondary lymphoid organogenesis during embryogenesis and for maintaining an organized secondary lymphoid structure during adulthood. The second set is OX40- and CD30-ligands, which are critical for memory T cell generation. Adult LTi cells regulate adaptive immune responses by providing LTbetaR signals to stromal cells to maintain secondary lymphoid tissue structure, and determine adaptive immune responses by providing OX40 and CD30 survival signals to activated T cells in memory T cell generation. Along with the consideration of the roles of embryonic LTi cells in primary and secondary lymphoid tissues, this review highlights the roles of adult LTi cells in secondary lymphoid tissue function.
Adult ; Animals ; Humans ; Lymphoid Tissue/cytology/embryology/*immunology ; Lymphokines/immunology/metabolism ; T-Lymphocytes, Helper-Inducer/cytology/*immunology/metabolism ; Thymus Gland/cytology/embryology/*immunology

OBJECTIVETo explore the mechanism of electroacupuncture of "Shuanggu Yitong" prescription on postponing aging.

METHODSForty 3-month SD rats, male only, 30 rats were made sub-acute aging model by D-galactose s.c. injection continuously for 42 d, and rest of the rats, 10, were divided into a normal control group. After the modeling, the sub-acute aging model rats were randomly into a Shuanggu Yitong group [electroacupuncture at "Guanyuan" (CV 4) and "Zusanli" (ST 36), hand needle at "Baihui" (GV 20)], an acupuncture control group [electroacupuncture at "Weizhong" (BL 40) and "Shuifen" (CV 9), hand needle at "Yintang" (GV 29)] and an aging model group, ten in each one. The treatment was given once in a day, six of which made a course. The rats in the normal control group and aging model group were not received any treatment. After the treatment for three weeks, the rats were put to death and their spleen index, thymus index and the T lymphocytes subgroups (CD8(+) T/T cell and CD8(+) CD28(-) T/CD8(+) T cell) were tested.

RESULTSThe spleen index (1.74 +/- 0.059) and thymus index (0.64 +/- 0.039) in the aging model group was obviously lower than those in the normal control group (1.93 +/- 0.061), (0.81 +/- 0.053) respectively (both P < 0.05); the CD8(+) CD28(-) T/CD8(+) T cell percentages (26.28 +/- 4.69)% and CD8(+) T/T cell percentages (43.33 +/- 2.84)% in the aging model group were both significantly higher than those (15.08 +/- 5.58)% (P < 0.01), (34.70 +/- 4.24)% (P < 0.01) in the normal control group. Compared with the aging model group, the spleen index (1.91 +/- 0.081) and thymus index (0.79 +/- 0.080) in the Shuanggu Yitong group were significantly higher (both P < 0.05), but obviously decreased with the percentage of CD8(+) CD28(-) T/CD8(+) T cell (18.07 +/- 1.73) (P < 0.01); the percentage of CD8(+) CD28(-) T/CD8(+) T cell (18.07 +/- 1.73)% in the acupuncture control group was also lower than the aging model group (P < 0.05), but more obvious reduce for the Shuanggu Yitong group (P < 0.05).

CONCLUSIONThe treatment of Shuanggu Yitong prescription could regulate the proportions of the T lymphocyte subset, and slow down the immunosenescence of subacute aging model rats induced by D-galactose.

Acupuncture Points ; Aging ; physiology ; Animals ; Electroacupuncture ; Flow Cytometry ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Spleen ; cytology ; T-Lymphocyte Subsets ; cytology ; Thymus Gland ; cytology

The aim of this study was to investigate the roles of chemokine CCL20 in development of CD4(+)CD25(+) thymocytes by means of fetal thymus organ culture. Fetal mouse thymus lobes were removed at the fetus age of 14.5 days and cultured in complete RPMI 1640 with 20% FBS in vitro. Phenotypes of the thymocytes were analyzed by FACS and the number of cells per lobe was counted. The results revealed that from day 14.5 to day 19, the absolute and relative numbers of the CD4(+)CD25(+) thymocytes varied similarly as their development as in vitro culture at 6 days. Data showed that during the 6 days in vitro culture the CD4(+)CD25(+) cell percentage out of CD4(+) cells was 58.29%, 12.14%, 6.08%, 17.78%, 9.06%, 4.04% and the CD4(+)CD25(+) cell percentage out of CD25(+) cells was 3.75%, 10.81%, 17.20%, 51.93%, 61.64%, 80.06%. All these data indicated similar characters to their development in vivo. Moreover, at interference with CCL20, the percentage of CD4(+)CD25(+) T cells in thymocytes significantly decreased at the 3 and 6 days from 3.24+/-0.18 and 3.96+/-0.24 to 1.27+/-0.11 (p<0.001) and 1.76+/-0.22 (p<0.001) respectively. It is concluded that the development of CD4(+)CD25(+) thymocytes is similar both in vitro and in vivo, interfering with CCL20 significantly downregulate the expression of CD4(+)CD25(+) T cells. The above data may help to understand the development of naturally arising CD4(+)CD25(+) regulatory T cells.
Animals ; Chemokine CCL20 ; pharmacology ; Embryo, Mammalian ; Embryonic Development ; Female ; Male ; Mice ; Mice, Inbred BALB C ; Organ Culture Techniques ; T-Lymphocytes, Regulatory ; cytology ; drug effects ; Thymus Gland ; cytology ; embryology

AIMTo observe the antiproliferative effect of antisense recombinant adenoviral vector for c-myc on rat thymus lymphocytes.

METHODSAntisense and sense bacterial plasmids for c-myc were constructed. Bacterial plasmids and El detected adenoviral plasmid were cotransfected into 293 cells. Recombinant adenoviral vectors were obtained after cotransfection. The antiproliferative effects were assayed by MTS. The expression of c-myc mRNA was detected by RT-PCR.

RESULTSThe results showed that antisense recombinant adenoviral vector for c-myc could inhibit rat thymus lymphocytes proliferation. The expression of c-myc mRNA was decreased after antisense recombinant adenoviral vector for c-myc was transfected into cells.

CONCLUSIONRecombinant antisense adenoviral vector for c-myc could inhibit rat thymus lymphocytes proliferation.

Adenoviridae ; genetics ; Animals ; Antisense Elements (Genetics) ; Cell Line ; Cell Proliferation ; Genes, myc ; genetics ; Genetic Vectors ; Lymphocytes ; cytology ; Rats ; Thymus Gland ; cytology

This study was purposed to investigate the effects of high-dose dexamethasone on structure and function of thymic epithelial cells (TEC). Male C57BL/6 mice aged 6 to 8 weeks were used as experimental animals. The mice were injected intraperitoneally with dexamethasone (20 mg/kg), and the other mice treated with saline were used as controls. Thymus was harvested at day 5 after treatment. The histological changes of the treated thymus were monitored by HE staining and in situ immunofluorescence staining. The ratio of each subset in the thymus were analyzed by using flow cytometry, and quantitative PCR was applied to detect the expression levels of IL-22 and Foxn1, which represent the regenerative function of thymus. The results showed that compared with control mice, the structure of TEC in mice treated with high-dose dexamethasone was damaged and the thymic cell number was declined dramatically (P < 0.05); the ratios of thymus cell subsets were changed, the number of double positive (DP) thymus cells among these subsets declined sharply (P < 0.05); the expression levels of Foxn1 and IL-22 increased by 34 and 8 folds respectively. It is concluded that the use of high-dose dexamethasone can lead to damage of the structure and function of TEC, and induce up-regulation of the expression of genes related to thymus repair.
Animals ; Dexamethasone ; administration & dosage ; adverse effects ; Epithelial Cells ; cytology ; drug effects ; Forkhead Transcription Factors ; metabolism ; Interleukins ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Thymus Gland ; cytology ; drug effects

OBJECTIVETo investigate the effect of transfusion of necrotic cells on regulatory T (Treg) and Th17 cell balance in septic mice.

METHODSThirty-four C57BL/6 mice were randomized into PBS group (n=5), sham-operated group (n=5), sepsis group (n=12), and necrotic cell transfusion group (n=12) and subjected to intraperitoneal PBS injection, sham operation by separating the cecum only, cecal ligation and puncture (CLP), and injection of 2 × 10⁷ necrotic cells 5 days before CLP, respectively. All the mice were sacrificed 2 weeks after CLP for analyzing the proportion of CD4⁺Foxp3⁺Treg cells and CD4⁺IL17A⁺Th17 cells in the peripheral blood, spleen and thymus by flow cytometry.

RESULTSThe percentage of Th17 cells and Treg/Th17 ratio in the spleen was significantly higher in CLP group than in the sham-operated group and PBS group (P<0.01). The percentage of Treg cells in the thymus was significantly lower in CLP group than in the sham-operated group (P<0.01). Pre-infusion of necrotic cells redressed the abnormality of Treg and Th17 cell percentages and Treg/Th17 imbalance in mice following CLP (P<0.05).

CONCLUSIONPre-infusion of necrotic cells can reverse Treg/Th17 imbalance in septic mice.

Animals ; Cecum ; Flow Cytometry ; Interleukin-17 ; Ligation ; Mice ; Mice, Inbred C57BL ; Necrosis ; Sepsis ; therapy ; Spleen ; T-Lymphocytes, Regulatory ; cytology ; Th17 Cells ; cytology ; Thymus Gland

BACKGROUNDVascular endothelial growth factor (VEGF) in the thymus was mainly produced by the thymic epithelial cells (TECs), the predominant component of the thymic microenvironment. The progression of TECs and the roles of VEGF in the neonatal thymus during sepsis have not been reported. This study aimed to explore the alterations of TECs and VEGF level in the neonatal thymus involution and to explore the possible mechanisms at the cellular level.

METHODSBy establishing a model of clinical sepsis, the changes of TECs were measured by hematoxylin-eosin staining, confocal microscopy, and flow cytometry. Moreover, the levels of VEGF in serum and thymus were assessed based on enzyme-linked immunosorbent assay and Western blotting.

RESULTSThe number of thymocytes and TECs was significantly decreased 24 h after lipopolysaccharide (LPS) challenge, (2.40 ± 0.46)×10 7 vs. (3.93 ± 0.66)×10 7 and (1.16 ± 0.14)×10 5 vs. (2.20 ± 0.19)×10 5 , P < 0.05, respectively. Cortical TECs and medullary TECs in the LPS-treated mice were decreased 1.5-fold and 3.9-fold, P < 0.05, respectively, lower than those in the controls. The number of thymic epithelial progenitors was also decreased. VEGF expression in TECs was down-regulated in a time-dependent manner.

CONCLUSIONVEGF in thymic cells subsets might contribute to the development of TECs in neonatal sepsis.

Animals ; Animals, Newborn ; Cells, Cultured ; Epithelial Cells ; cytology ; drug effects ; metabolism ; Lipopolysaccharides ; toxicity ; Mice ; Thymus Gland ; cytology ; drug effects ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism