Thymus最新文献

{"title":"Modulation of cytokine gene expression by thymic lympho-stromal cell to cell interaction: effect of retinoic acid.","authors":"M Napolitano,&nbsp;D Bellavia,&nbsp;M Maroder,&nbsp;M Farina,&nbsp;A Vacca,&nbsp;L Frati,&nbsp;A Gulino,&nbsp;I Screpanti","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have examined the expression of a panel of cytokines in thymic epithelial cells and CD4-CD8- (DN) thymocytes following cell to cell lymphostromal interaction, in an experimental model which enhances in vitro thymocyte maturation. Since retinoic acid (RA) has been previously shown to be an inhibitor of thymocyte maturation process in this model, we wanted to analyse cytokine expression in DN thymocytes and thymic epithelial cells following the RA-induced impairment of in vitro thymocyte maturation. Cell to cell lymphostromal interaction results in increased IL2 and decreased IL7 expression in thymocytes while the expression of IL1 beta and IL7 increased and decreased, respectively, in thymic epithelial cells. Addition of RA to lympho-stromal cell co-culture results in the enhancement of IL4 and IL7 expression in thymocytes while in thymic epithelial cells IL1 alpha decreased and IL6 and IL7 increased. These data indicate that discrete patterns of cytokine expression are present in thymocyte precursors and in thymic epithelial cells during in vitro T-cell development. They furthermore suggest that specific cytokine modulation might contribute to the RA-induced impairment of thymocyte differentiation.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"24 4","pages":"247-58"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20417512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thymic interdigitating cells express thioredoxin (TRX/ADF): an immunohistochemical study of 82 thymus and thymoma samples.","authors":"T Go,&nbsp;N Isowa,&nbsp;T Hirata,&nbsp;J Yodoi,&nbsp;S Hitomi,&nbsp;H Wada","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Thymic ID cells are involved in the differentiation of mature T cells which are resistant against apoptosis. TRX/ADF is a potent thiol-related reducing agent, acts as a redox regulator, and it can attenuate the induction of apoptosis of T lineage lymphocytes. In the present study, 42 thymoma-free thymus and 40 thymoma samples were examined to identify the expression of TRX/ADF in human thymic tissue. TRX/ADF high-producer (TRXh) cells with cytoplasmic protrusions were found distributed in the thymic medulla. These TRXh cells were negative for CD3, a lymphocyte marker, keratin, an epithelial cell marker, and CD68 or lysozyme, macrophage/monocyte markers, but were positive for S100 protein and HLA-DR complex. Our results revealed that the TRXh cells in the thymic medulla were ID cells. As TRX/ADF has an important and fundamental role in cellular responses acting against oxidative stress, TRX/ADF may provide an explanation of cellular interaction between the medullary ID cells and the mature T cells.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"24 3","pages":"157-71"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20099012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thymic stromal cells eliminate T cells stimulated with antigen plus stromal Ia molecules through their cross-talk involving the production of interferon-γ and nitric oxide","authors":"邰 旭光","doi":"10.11501/3109933","DOIUrl":"https://doi.org/10.11501/3109933","url":null,"abstract":"We previously established a thymic stromal cell clone capable of inducing differentiation of immature thymocytes and described a clonal elimination model in which T cell clones are killed on the monolayer of this stromal clone by stimulation of their T cell receptors (TCR) with antigen plus stromal Ia molecules. This study investigated molecular mechanisms underlying this phenomenon. Antigenic stimulation on thymic stromal cells produced large amounts of interferon-gamma (IFN-gamma) and small amounts of tumor necrosis factor-alpha (TNF-alpha). Addition of anti-IFN-gamma monoclonal antibody (mAb) to these cultures largely prevented death of TCR-stimulated T cells. T cell death was also induced when cultures were treated with recombinant IFN-gamma (rIFN-gamma) or rTNF-alpha instead of the relevant antigen, showing that these lymphokines are involved in the process of T cell death. It was further demonstrated that these lymphokines, especially IFN-gamma, induced the expression of mRNA for the inducible type of nitric oxide (NO) synthase in thymic stromal cells and that enhanced levels of NO were produced by stromal cells cultures with T cells plus antigen or stimulated with rIFN-gamma or rTNF-alpha. NO was found to be critically responsible for inducing T cell death on the stromal cell monolayer following stimulation of T cells with antigen or of stromal cells with rIFN-gamma or rTNF-alpha, because T cells death was completely prevented by addition of NG-monomethyl-L-arginine (L-NMMA), which is capable of inhibiting NO production. These results indicate that elimination of TCR-stimulated T cells on thymic stromal monolayers with the capacity to support thymocyte differentiation is induced by the cross-talk between IFN-gamma/TNF-alpha-producing T cells and stromal cells capable of producing NO in response to these lymphokines.","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"1996-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64438189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naturally-occurring anti-thymocyte autoantibody which identifies a restricted CD4+CD8+CD3-/lo/int thymocyte subpopulation exhibits extensive polyspecificity.","authors":"J R Underwood,&nbsp;A McCall,&nbsp;X F Csar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In this study, naturally-occurring, monoclonal IgM kappa anti-thymocyte autoantibodies from the neonatal inbred Balb/c mouse-derived hybridoma NMT-1 (NMT-1 mAb), previously reported to identify a restricted CD4+CD8+CD3/lo/int thymocyte subpopulation, have been shown to exhibit extensive polyspecificity. Using immunofluorescence, immunoblotting and antibody titration and competition ELISAs, NMT-1 mAbs exhibited polyspecific binding to 12 apparently structurally unrelated self and non-self antigens. The autoreactive component of the polyspecificity profile of NMT-1 mAbs encompassed reactivity to developmentally-related 14.5 and 18.3 kDa Thy-1 glycoforms expressed on a CD4+CD8+CD3-/lo/int thymocyte subpopulation. The autoreactivity profile of NMT-1 mAbs also included recognition of the heavy and light chains of mouse IgG1 and mouse cytokeratins within thymic medullary epithelium and basal epithelial cells of stratified squamous epithelium of mouse tongue, oesophagus, stomach, skin and vagina. Examination of the polyspecificity profile of NMT-1 mAbs was also undertaken using a panel of 23 antigens including heterologous proteins, phospholipids, haptens and bacterial antigens by antibody titration and competition ELISAs. Antibody titration ELISAs demonstrated that NMT-1 mAbs bound nine antigens including bovine carbonic anhydrase, ovalbumin, cardiolipin, phosphatidylserine, the haptens, DNP and FITC and the bacterial antigens including Escherichia coli beta-galactosidase and the toxoids from Corynebacterium tetani and Clostridium diphtheria. Competition ELISAs, based on the inhibition of NMT-1 mAb binding to antigens adsorbed to ELISA plate surfaces by inhibitor antigens in solution, demonstrated that NMT-1 mAb interactions were not dependent on multivalent binding. In these assays, NMT-1 mAbs recognized unmodified (native) epitopes on the solution phase forms of the protein antigens, including E. coli beta-galactosidase and toxoids from Corynebacterium tetani and Clostridium diphtheria, providing further evidence for the hypothesis that the binding of multiple, apparently unrelated, antigens by NMT-1 mAbs occurs via unique polyspecific antigen combining sites.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"24 2","pages":"61-88"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19701517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-1, ICAM-1, LFA-3, and hydrocortisone differentially regulate cytokine secretion by human fetal thymic epithelial cells.","authors":"S Shu,&nbsp;P Naylor,&nbsp;J L Touraine,&nbsp;J W Hadden","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Human fetal thymic epithelial cells (TEC) were cultured under serum-free conditions. The TEC were analyzed for the secretion of 14C-labelled peptides and of IL-3, IL-6 IL-7, IL-8, GM-CSF, LIF, fibronectin and thymosin alpha 1 by ELISA tests. IL-3 and IL-7 were not detected from these TEC. Lack of IL-7 and presence of thymosin alpha 1 and of the surface molecule TE-4 depicts these cells as subcapsular/medullary TEC. TEC secreted constitutively IL-6, IL-8, fibronectin and thymosin alpha 1 but not GM-CSF of LIF. Stimulants included recombinant IL-1 and monoclonal antibodies to the surface adhesion molecules ICAM-1 and LAF-3. In addition, hydrocortisone (2.7 x 10(-7) M) was used to dissect secretion patterns. Recombinant IL-1, anti ICAM-1, and anti LFA-3 alone and collectively induced modest but significant increases in the secretions of 14C-labelled peptides and of IL-6 and IL-8 which were not inhibited by HC. Recombinant IL-1 but not anti ICAM-1 and anti LFA-3 induced GM-CSF and LIF. HC inhibited the secretion of GM-CSF and LIF induced by IL-1. None of the stimulants augmented the constitutive secretion of fibronectin or thymosin alpha 1 and HC inhibited thymosin alpha 1 secretion. TEC secretion of cytokines but not thymosin alpha 1 and fibronectin appear to be regulated in a more complex manner than heretofore recognized.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"24 2","pages":"89-99"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19701518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased numbers of CD5+ B cells in the thymus of estradiol benzoate-treated rats.","authors":"A Martín,&nbsp;A Vicente,&nbsp;M Torroba,&nbsp;C Moreno,&nbsp;E Jiménez,&nbsp;A G Zapata","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the present work we combine both flow cytometry and in situ immunohistochemical techniques to study the changes affecting a minor B cell population described within the normal rat thymus, after treatment with estradiol benzoate (EB). Our results, in agreement with previous data, show that the vast majority of these intrathymic B cells are CD5+. The existence of CD5+ B cells was confirmed flow cytometrically in both cervical lymph nodes and spleen of control, adult Wistar rats. Moreover, after EB administration intrathymic B cells increased significantly especially in those rats receiving 500 micrograms of EB, constituting cell masses around the blood vessels of cortico-medullary area and in the thymic medulla. We discuss the significance of this increased number of intrathymic CD5+ B cells, which is probably due to a selective cell migration from the periphery into the thymus, from the view of the effects of estradiol on the thymic vascular permeability.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"24 2","pages":"111-27"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19701520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclic adenosine monophosphate (cAMP) differentially regulates IL-4 in thymocyte subsets.","authors":"S Wirth,&nbsp;M Lacour,&nbsp;F Jaunin,&nbsp;C Hauser","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>It was recently reported that cAMP upregulated IL-4 in T cell lines generated in vitro and expressing an unrestricted lymphokine pattern. In order to study the effect of cAMP on IL-4 released by freshly isolated T cell populations, we tested various T cell subsets that have previously been reported to synthesize this lymphokine. We found that cAMP upregulated IL-4 release from in vivo activated single CD4+ peripheral T cells and CD4+CD8-HSAlowNK1.1- thymocytes stimulated with ionomycin and phorbol ester. Furthermore, as in conventional single CD4+ or CD8+ thymocytes, cAMP enhanced IL-4 production in CD4+CD8-NK1.1+ thymocytes. This latter subset has recently been shown to belong to a independent T cell lineage that is positively selected by MHC class I molecules, recognizes CD1 and expresses a restricted T cell receptor repertoire. In contrast, cAMP appeared not to upregulate IL-4 in a third independent T cell lineage. This was suggested by the observation that cAMP did not increase IL-4 in CD3+CD4-CD8- thymocytes, which are thought not to give rise to conventional single CD4+ or CD8+ T cells. It therefore appears that cAMP is coupled differently to IL-4, depending on the T cell lineage. In contrast, in all IL-4 producing stages of conventional T cells, IL-4 is consistently upregulated by cAMP.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"24 2","pages":"101-9"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19701519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thymic selection of immunoglobulin idiotype specific T-cells.","authors":"Z Dembić,&nbsp;S Weiss,&nbsp;B Bogen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The thymus is the major site for differentiation and maturation of developing T-cells. The diversity in the T-cell repertoire is generated during ontogeny by rearrangements of T-cell receptor gene segments that encode clonally distributed receptors. Most of the newly produced thymocytes that bear alpha beta TCR die in the thymus as a consequence of at least two selective processes. Those that can react to self MHC antigens survive (positive selection), but only if the binding affinity for the same or other self MHC (probably complexed with self peptides) molecules is not too high (negative selection). As a result, each T-cell that has acquired functional competence in the thymus should have a certain degree of self-MHC specificity. Our comprehension of thymic development has been aided by the study of transgenic mice that bear functionally rearranged TCR or Ig lambda light chain genes. To study positive selection we analyzed transgenic mice with alpha beta TCR genes isolated from a T-cell clone specific for an idiotypic peptide of lambda 2(315) (a mutant of the lambda 2 Ig chain) bound to the E(d) MHC class II molecule. The results suggest that positive selection of some thymocytes might be weak, reminiscent of a 'struggle for survival', since the selected population was small and had high levels of transgenic receptor and coreceptor (CD4) molecules. The thymic tolerance mechanism was also investigated using a combination of both TCR and lambda 2(315) transgenic mice. The clonal deletion of Id specific thymocytes was influenced by the production site as well as the concentration of the lambda 2(315) antigen. In conclusion, the interaction avidity of a single thymocyte, which is important for selective processes, might be affected by the expression levels of each interacting component: TCR, CD4 or CD8 and MHC molecule and self antigen.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"22 3","pages":"141-52"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18937164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of antigens homologous to human retrovirus molecules in normal and severely atrophic thymus.","authors":"W T Dura,&nbsp;B M Wozniewicz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>An immunopathologic study of normal and severely atrophic thymuses (STA) was undertaken in order to evaluate the expression of human retrovirus (envelope and core) molecules in thymic epithelial cells (TEC) in HIV negative children. Both normal and STE thymuses disclosed p19, p24, p39, p45 and p55 viral core proteins as well as gp46, gp63 glicoprotein of envelope origin. No evidence of gp160, gp120 and gp41 molecules were observed in TEC which suggested endogenous lack of receptor molecules for HIV. The results are discussed in the context of possible thymus oriented autoimmune reaction in HIV and non-HIV bearing patients and in consequence, severe injury of TEC forming microenvironment.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"22 4","pages":"245-54"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18984212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of a multidrug chemotherapy regimen on the thymus.","authors":"G A Perry,&nbsp;J D Jackson,&nbsp;J E Talmadge","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Multidrug chemotherapy regimens are commonly used in the treatment of cancer. The dose limiting tissue for chemotherapeutic treatment is often the bone marrow, as many chemotherapeutic agents selectively target rapidly proliferating cells. Bone marrow transplantation (BMT) has allowed an increase in chemotherapeutic dose; however, this type of therapy is associated with a prolonged suppression of immune function following the BMT. Although it may be possible to augment this immune function, animal models which can be used to test various cytokines have not been well described. We have developed a mouse model of multi-drug chemotherapy which, like the human, demonstrates long term immune suppression following BMT. In this report, we describe the specific effects of this chemotherapy regimen on T cell differentiation in the thymus of treated mice using three color FACS analysis. Results demonstrated that specific populations of thymocytes are extremely susceptible to chemotherapeutic insult. Both thymus cellularity and the immature CD3-CD4+CD8+ double positive population dropped to approximately 3% of their original values by 7 days after chemotherapy initiation. During the same time period, cells expressing both alpha beta and gamma delta T cell receptors demonstrated a 2-6 fold increase in frequency. Similar results were observed for the alpha beta+ CD4-CD8- population of natural suppressor cells. Long-term changes in the proportion of cells expressing the V beta 5 TCR were also observed following chemotherapy. These results demonstrate that chemotherapy regimens may directly influence T cell differentiation within the thymus, and also suggest that long term changes in the T cell V beta repertoire may occur following chemotherapy.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"23 1","pages":"39-51"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18861367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}