{"title":"Unravelling human T-cell receptor junctional region sequences.","authors":"T M Breit, J J Van Dongen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Careful analysis of functional V delta 2-J delta 1 and V gamma 9-J gamma 1.2 rearrangements of peripheral T-lymphocytes showed high frequencies of leucine and valine at a fixed position in the V delta 2-J delta 1 junctional regions. This phenomenon remained unnoticed in the numerous published junctional regions for over several years. Because comparable preferential motifs might also occur in junctional regions of other T-cell populations in health and disease, more precise analysis of junctional region diversity is needed. For this reason we describe general guidelines for identification of the various elements in TcR junctional regions: D-gene-derived nucleotides (in case of TcR-beta and TcR-delta genes), P-region nucleotides, N-region nucleotides, and deletion of nucleotides by trimming of the rearranged gene segments. In addition, we summarized the known genomic germline sequences of rearranging TcR gene segments, which are necessary for proper application of the general guidelines. Subsequent analysis of the majority of published TcR junctional regions, allowed us to determine the composition and average insertion and deletion of nucleotides in genomic junctional regions. Because the protein junctional region instead of the genomic junctional region determines the actual specificity of TcR chains, the amino acid composition of the protein junctional regions of different types of TcR gene rearrangements was determined. This revealed some unexpected characteristics, such as the virtual absence of cysteine in all functional TcR junctional regions and increased or decreased frequencies of particular amino acid residues in specific TcR junctional regions. Application of the guidelines in combination with the summarized TcR germline sequences may contribute to uniformity in the analysis of junctional regions and may lead to important information concerning TcR specificity.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"22 3","pages":"177-99"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18937002","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":"Role of thymic stromal cells in thymocyte education: a comparitive analysis of different models.","authors":"A Martín-Fontecha, H J Schuurman, A Zapata","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The thymus is the privileged lymphoid organ for T-cell differentiation, including clonal selection. Precursor thymocytes are selected on the basis of their ability to recognize self-major histocompatibility complex molecules (MHC) that are expressed on thymic stromal cells, including epithelial cells, macrophages, and interdigitating cells/dendritic cells (IDCs/DCs). Epithelial cells have been associated with positive selection, and dendritic cells with negative selection, but the exact role played by these stromal elements is still unresolved. This review focuses on the different in vitro and in vivo approaches that have been used to elucidate the role of thymic stromal cell types in thymic function, and on a critical evaluation of these approaches.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"22 4","pages":"201-13"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18984208","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":"Programming for recognition and programming for response. Separate developmental subroutines in the murine thymus.","authors":"E V Rothenberg, R A Diamond, D Chen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Pre-T cells become programmed with the capacity to make functional responses to activating stimuli in a process that occurs prior to, and independently of, T-cell receptor gene rearrangement and T-cell receptor-dependent positive selection. In spite of this early programming, as differentiation proceeds further the cells enter a stage in which they appear to be unable to make any functional responses. This 'eclipse' phase begins when the cells undergo successful T-cell receptor beta-chain rearrangement and ends, with the return of their functional competence, only when they successfully traverse positive selection. These results suggest that pre-T cells are subject to two distinct subroutines of differentiation, which cannot operate at the same time: one which confers function and one which confers and selects recognition specificity. To provide a possible molecular basis for the relationship between these two processes, we consider specific alterations in response-associated transcription factors that may cause the changes in responsiveness observed during programming for recognition. The interplay of the two differentiation subroutines is proposed to be a consequence of the use of common transcription factors in different combinatorial contexts for functional responses, assembly of T-cell receptor complexes, and selection.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"22 4","pages":"215-44"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18984209","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":"Differential effects of T cell receptor ligation of TCR gamma delta thymocyte development in fetal thymic organ culture.","authors":"Y Tatsumi, D Deluca, R Q Cron, J A Bluestone","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Fetal thymus organ culture system (FTOC), a well-known model used for the study of TCR alpha beta development, was employed to study TCR gamma delta cell development. It was found that different waves of TCR gamma delta cells develop from precursors within the fetal thymi at the time in vitro culture. Subsets of fetal thymocytes were analyzed by flow cytometry and 2-D gel biochemical analysis was performed. After 5 days in FTOC, V gamma 3+ and V gamma 2+ cells were dominant. By day 12 FTOC, the absolute number of V gamma 3+ cells decreased while V gamma 2+ and V gamma 4+ cells became dominant. These observations suggest that the thymic micro-environment affects the thymic waves of TCR gamma delta subsets. Furthermore, the effect of TCR/antigen interaction in the development of TCR gamma delta cells was examined with anti-TCR mAbs added into the FTOC. Anti-CD3 mAb added to day 5 and day 12 FTOC inhibited TCR gamma delta development, especially V gamma 4+ cells. On the other hand, V gamma 2+ cells were relatively resistant to the addition of anti-TCR mAb. The reduction of TCR gamma delta+ thymocytes was not due to the modulation of TCR molecules and could be reversed by Cyclosporin A (CsA). These results suggest that TCR ligation negatively regulates the development of TCR gamma delta cells in a V gamma-specific manner.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"23 3-4","pages":"131-53"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19505908","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":"Developmental regulation of cAMP signaling pathways in thymocyte development.","authors":"L J Scherer, R A Diamond, E V Rothenberg","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Major developmental transitions in thymocyte differentiation are accompanied by sharp alterations in cAMP metabolism. We have analyzed the cAMP accumulation responses of cell populations representing successive stages of T-cell development, namely: immature TcR- thymocytes from SCID mice, proliferating cortical blasts, small cortical thymocytes, medullary thymocytes and peripheral T cells. We find that all classes of thymocytes exhibit higher cAMP synthesis in response to forskolin than peripheral T cells. In immature TcR- thymocytes, this high capacity is buffered by efficient phosphodiesterase activity, but in CD4+CD8+TcRlow thymocytes, phosphodiesterase activity becomes much less effective. Phosphodiesterase activity then rises again after positive selection. The ability of thymocytes to respond to prostaglandin E is regulated distinctly from their ability to respond to forskolin. Unlike forskolin, PGE1 induces cAMP synthesis to similar levels in all classes of thymocytes, possibly due to partial activation of phosphodiesterase in cortical thymocytes by PGE1. Finally, we report a novel effect of Ca2+/protein kinase C signaling on cAMP accumulation, which occurs selectively in the proliferating cortical blasts.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"23 3-4","pages":"231-57"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19506498","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":"Corticosteroid treatment and X-ray irradiation in adult rats induce the reexpression of fetal markers in cortical thymic epithelial cells.","authors":"S Stojanović, V Dragojević-Simić, M Colić","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The phenotype of cortical thymic epithelial cells (TEC) following hydrocortisone-treatment and sublethal X-ray irradiation in adult rats was studied by immunohistochemistry. It was found that during thymic regeneration (2-16 days) a TEC subset, predominantly in the outer cortex, transiently expressed cytokeratin (CK) 19 and an antigen defined by PT13D11 monoclonal antibody (mAb). These markers are characteristic for fetal, but not adult cortical TEC. To examine whether regenerating thymocytes may influence the phenotype of cortical TEC we cultivated a rat cortical TEC line (R-TNC 1.1) with thymocytes isolated from the thymuses at day 7 after hydrocortisone treatment. The R-TNC 1.1 TEC line, although established from adult rat thymus, constitutively expresses PT13D11, but not CK19. The appearance of CK19 in the R-TNC 1.1 cells was not inducible neither by coculture of this line with thymocytes, nor by the influence of IL-1, IL-2, IL-6, TNF-alfa and IFN-gamma. These results demonstrated the phenotypic plasticity of cortical TEC in adult rats.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"24 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19607753","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":"Signal transduction defect in the acquired immunodeficiency syndrome and AIDS-related complex.","authors":"S Gupta","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Peripheral blood mononuclear cells from patients with the acquired immunodeficiency syndrome (AIDS), AIDS-related complex (ARC), and heterosexual controls were stimulated with anti-CD3 monoclonal antibody, phorbol myristate acetate (PMA), or both and 3H thymidine incorporation and IL-2 receptor (IL-2R alpha; CD25; Tac antigen) expression were measured. In addition, basal plasma membrane potential and plasma membrane potential following anti-CD3 stimulation were compared between the three groups. A significantly reduced DNA synthesis and CD25 expression was observed in both AIDS and ARC upon stimulation with anti-CD3 or PMA. Although, a significant synergism was observed with anti-CD3 plus PMA stimulation in both AIDS and ARC, and the responses were normalized to the levels of anti-CD3 or PMA response in normal control, the levels were significantly lower than those observed with anti-CD3 plus PMA in controls. Plasma membrane potentials were decreased (membrane depolarized) in both ARC and AIDS (AIDS > ARC), and anti-CD3 had no effect on further depolarization of plasma membrane in AIDS. These data suggest a defect in signal transduction pathway in patients with HIV-1 infection.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"22 2","pages":"83-90"},"PeriodicalIF":0.0,"publicationDate":"1993-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19199075","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":"NADPH-diaphorase positive cells in the chick and rat thymus.","authors":"P Gulati, A S Chan, S K Leong","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Nicotinamide-adenine dinucleotide phosphate-diaphorase (NADPH-d) positive cells were demonstrated in the medulla of the rat and chick thymus at light microscopic level. The NADPH-d positive cells were present as clusters and were predominantly localized near the corticomedullary boundary. These clusters were closely associated with the thymic cysts. Some cells were seen in close proximity to blood vessels. The presence of nitric oxide (NO) as indicated by the positive NADPH-d reaction in the cells forming the wall of the thymic cyst suggests a modulatory influence of NO over the activities of these cells. Other possible functions of NO are also discussed.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"22 2","pages":"117-24"},"PeriodicalIF":0.0,"publicationDate":"1993-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18523006","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":"Athymic (nude) mice fail to delete functional self-reactive helper T cells.","authors":"M J Caulfield, D Stanko, D D Isaak","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have examined the thymic requirement for the antibody response to a foreign antigen coupled to self erythrocytes. We find that self erythrocytes mediate thymus-independent, carrier specific help for the antibody response to the pneumococcal cell wall polysaccharide antigen, PnC. Thus, athymic nude mice gave a high primary antibody plaque-forming cell (PFC) response to PnC-mouse RBC but a low response to PnC coupled to sheep or burro RBC. The meager response to PnC coupled to foreign RBCs could not be attributed to antigenic competition since the response to the carrier (burro RBC) was < 100 PFC per spleen. Reconstitution of nude mice with splenic T cells from euthymic mice enhanced rather than suppressed the antibody response to PnC-mouse RBC. The results document that in the absence of thymic deletion, functional self-reactive helper cells persist in the nude mouse.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"22 2","pages":"91-6"},"PeriodicalIF":0.0,"publicationDate":"1993-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19199076","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":"HMG box proteins in early T-cell differentiation.","authors":"M Oosterwegel, M van de Wetering, H Clevers","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The central theme of this review is the molecular basis for commitment of cells to the T-cell lineage. Principles of transcriptional regulation are illustrated by two examples; the role of GATA-1 during erythroid differentiation and the function of MyoD-like proteins in myogenesis. Several regulatory proteins have been described in the T-cell lineage. Here, we focus attention on the HMG box family of DNA binding proteins. This recently defined family can be divided in two subfamilies: the HMG/UBF and the TCF/SOX group. The first group contains at least two HMG boxes and binds DNA non-specifically, while the other group of proteins has one HMG box and interacts with DNA sequence-specifically. Characteristics of the most prominent members of both subfamilies will be discussed. In particular, we will address the role of HMG box proteins in controlling the expression of T-cell specific proteins during differentiation.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"22 2","pages":"67-81"},"PeriodicalIF":0.0,"publicationDate":"1993-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19199072","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}