The Journal of molecular and cellular immunology : JMCI最新文献

{"title":"The in vivo behavior of T cell clones: altered migration due to loss of the lymphocyte surface homing receptor.","authors":"M O Dailey,&nbsp;W M Gallatin,&nbsp;I L Weissman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Although cloned lines of T lymphocytes have been valuable in defining the in vitro functions of well-defined cell types, they have often demonstrated relatively poor activity in vivo. One striking property of T cells clones which might affect their in vivo activity is their unusual inability to localized in lymphoid tissue as do most normal T cells. Normal lymphocyte recirculation and localization requires that lymphocytes recognize and pass through the walls of specialized high endothelial venules (HEV) as they enter into lymph nodes. We previously showed that murine T cell clones are unable to home into the peripheral lymphoid organs-lymph nodes and Peyer's patches. The inability of these cells to recognize lymph node HEV in an in vitro frozen section adherence assay suggested that the lack of lymphoid homing was due to the loss of a normal lymphocyte surface receptor for HEV. The present experiments were designed to determine: 1) the molecular mechanism responsible for the loss of normal lymphocyte migration, and 2) whether these migration and homing characteristics are irreversible features of T cell clones. Flow cytometric analysis of helper and cytolytic clones using a monoclonal antibody (MEL-14) specific for the lymphocyte homing receptor showed that they lack this surface receptor. This lack of receptor expression was confirmed by the inability to detect the antigen in detergent-solubilized extracts of surface-radiolabeled cells. Thus, the lack of homing to lymph nodes appears to be due to the loss of expression of the surface receptor which mediates the interaction between lymphocytes and HEV. When clones were rested in vitro in a nonproliferative state without stimulation by antigen or growth factors, they did not regain expression of the surface homing receptor or the ability to migrate to lymph nodes in vivo. The lack of receptor expression, therefore, is not merely associated with a rapidly proliferating state, but rather seems to be an irreversible feature of T cell clones, at least under in vitro culture conditions. T cell clones, both rested and recently restimulated, share certain features characteristic of activated T cells, as shown by recent results with MLC-stimulated T cell blasts. Both populations are large, brightly PNA-positive lymphocytes which lack expression of the MEL-14 receptor and do not home to peripheral lymphoid tissue. We propose that this PNA-high, MEL-14- nonrecirculating phenotype may represent a normal phase of T cell differentiation through which many T cells pass after being activated by specific antigen.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 1","pages":"27-36"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14112074","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":"The role of suppressor cells in maintaining tolerance to self molecules--a commentary.","authors":"P M Flood","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 3","pages":"140-2"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14112076","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":"The putative I-Jk- strain AKR/J synthesizes I-Jk+ molecules: implications for Jt gene control of I-J expression.","authors":"P M Flood,&nbsp;D B Murphy","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>At present, the genetic basis for control of murine I-J determinants is unknown. On one hand, it is clear that polymorphism in I-J molecules is controlled by genes mapping in the I region of the H-2 gene complex on chromosome 17. On the other hand, molecular genetic studies provide evidence that I-J molecules are not encoded by I region genes. Although formal proof of the latter must await isolation and characterization of I-J structural genes, these observations are compatible with the concept that I-J molecules are encoded by non-H-2 genes, but the expression of these non-H-2 genes is regulated or influenced by I region genes. Recent studies by Hayes et al. provide evidence for non-H-2 control of the cell surface expression of I-Jk determinants in strain AKR/J. This strain typed I-Jk-, as judged by complement dependent cytolysis with monoclonal I-Jk antibodies. Studies with recombinant inbred and congenic strains suggested that the I-Jk- phenotype in strain AKR/J was controlled by a gene (Jt) mapping on chromosome 4. Based on these observations and studies with F1 hybrids and numerous other strains, Hayes et al. concluded that interaction between the Jt gene and an H-2 gene on chromosome 17 (probably E beta or E alpha) regulates the production and expression of I-Jk molecules, and hypothesized that I-Jk epitopes may reside on Jt modified Class II molecules or on the Jt gene product.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 2","pages":"95-103"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14112563","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":"Human and murine interleukin 1 possess sequence and structural similarities.","authors":"P E Auron,&nbsp;L J Rosenwasser,&nbsp;K Matsushima,&nbsp;T Copeland,&nbsp;C A Dinarello,&nbsp;J J Oppenheim,&nbsp;A C Webb","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The molecular cloning and sequence analysis for human and murine interleukin 1 precursor have recently been described. Comparison of the amino acid sequences resulting from these data can be used to aid in the identification of conserved regions essential to biological activity. We report results which confirm the relationship between these two molecules and suggest that specific regions may be essential for activity. Amino terminal sequence analysis of a 19,000 Mr biologically active IL-1 isolated from stimulated human monocytes reveals a sequence which is in good agreement with that inferred from the human cDNA and, furthermore, locates the processed amino terminus at a site similar to that described for the murine sequence.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 3","pages":"169-77"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14997047","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":"The reorientation of the Golgi apparatus and the microtubule-organizing center in the cytotoxic effector cell is a prerequisite in the lysis of bound target cells.","authors":"A Kupfer,&nbsp;G Dennert,&nbsp;S J Singer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This investigation is concerned with the detailed mechanisms of cytotoxicity, and in particular, with early cell surface and intracellular events that occur upon the binding of a cytotoxic effector cell to its susceptible target. In earlier studies, we have shown by immunofluorescence microscopy that when cloned natural killer (NK) and cytolytic T lymphocyte (CTL) cells bind to susceptible target cells, a rapid and coordinate reorientation of the perinuclear Golgi apparatus and the microtubule-organizing center (MTOC) occurs inside the effector cell so that the two organelles face the bound target. It was proposed that the purpose served by this reorientation is to direct Golgi-derived secretory vesicles, containing one or more cytotoxic components, to the area of target cell binding. In order to establish more firmly that this reorientation of the two organelles is an essential early event in cytotoxicity, we have performed three different types of experiments. 1) Upon binding cloned effector cells to susceptible targets in the presence of Mg+2 but absence of Ca+2, conditions in which no killing occurs, we found that no reorientation of the MTOC in the effector cell is induced; however, the addition of CA+2 to these cell couples results in a rapid MTOC reorientation. 2) With a lysis-defective subclone derived from a cytolytic NK clone, binding to target cells did not induce an MTOC reorientation in the defective killer cell. 3) In multitarget conjugates formed with single CTL, the MTOC in the CTL was oriented to face that one target cell which was in the process of lysis at the time. These results, together with our earlier findings, strongly indicate that a Golgi/MTOC reorientation inside the target-bound effector cell is a pre-requisite for the effective lysis of the target. They also reveal the existence, previously unrecognized, of a specific signaling mechanism from the viable target cell to the effector cell, which must be involved in the triggering of this Golgi/MTOC reorientation. These conclusions are consistent with the proposal that a polar cytotoxic secretory mechanism is responsible for target cell lysis.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 1","pages":"37-49"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14997213","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":"Lymphocytes: the Third World.","authors":"C A Janeway","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 2","pages":"57-9"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14996526","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":"Evidence for defects in accessory and T cell subsets in mice expressing the xid defect.","authors":"C Clayberger,&nbsp;R H DeKruyff,&nbsp;R Fay,&nbsp;B Huber,&nbsp;H Cantor","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mice expressing the X-linked recessive CBA/N genetic defect xid lack a subpopulation of B cells which appears late in normal B cell ontogeny and is characterized by expression of the cell surface antigens Lyb3, Lyb5, and Lyb7. In adult mice with the xid defect, responses to Type 2 antigens such as TNP-ficoll are entirely absent and responses to Type 1 antigens such as TNP-LPS are somewhat reduced. Primary in vitro responses to the T dependent antigen sheep red blood cells (SRBC) are defective but secondary responses are normal. These and other findings have led to the hypothesis that one effect of the xid defect is the inability of a subset of B cells to respond to nonspecific signals from T cells or accessory cells. The cellular basis of the xid defect is not well understood. The simplest explanation is that it reflects a primary lesion in the development of a subpopulation of B cells responsible for the types of immune responses described above. An alternative notion is that the xid defect is expressed primarily in a non-B cell population (e.g., T cells or accessory cells) which are necessary for the development and/or function of this B cell subset. A direct approach to this problem depends on the availability of homogeneous populations of B cells, T cells, or accessory cells. Recently we have described a cloned dendritic cell, Den-1, which is a potent stimulator of some B and T cell responses.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 2","pages":"61-9"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"15031982","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":"Small and large B cells respond differently to T cell-derived B cell growth and differentiation factors.","authors":"J E Layton,&nbsp;P H Krammer,&nbsp;T Hamaoka,&nbsp;J W Uhr,&nbsp;E S Vitetta","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A major problem in B cell biology is the determination of the roles played by helper T (TH) cells vs cytokines in the activation, replication, and differentiation of B lymphocytes. There is general agreement that activated B cells in cycle can replicate and terminally differentiate when provided with appropriate T cell-derived lymphokines. There is considerable controversy, however, as to whether cytokines can induce resting G0 B cells to secrete IgM. Some reports claim that TH cells are required before cytokines can act. In contrast, other reports claim that some T cell-derived supernatants (SN) have the capacity to activate resting B cells to become immunoglobulin-secreting cells. In the present study, we have examined one such SN (S26.5) as well as the EL-4 and PK 7.1 SN for their capacity to activate resting G0 B cells and a population of less dense B cells containing activated cells. These two populations, separated by Percoll density centrifugation, were characterized for size, stage in the cell cycle, and cell surface phenotype. It was shown that the most dense population contained predominantly G0 B cells, whereas the less dense population contained a subset of cells in cycle. Our studies show that neither T cell SN nor, indeed, any combination of cytokines and anti-immunoglobulins caused a major increase in the number of cells secreting IgM in the population enriched in G0 cells. In contrast, the T cell SN caused marked increases in the generation of IgM secreting cells in the population that contained a large proportion of activated cells. Limiting dilution analysis confirmed that the number of responding cells in the dense cell population was substantially lower than the number of responding cells in the less dense population. The small number of precursors in the dense B cell population may be attributed to contamination of that population with cells that have undergone activation steps in vivo. The present results, therefore, add further evidence to an existing large body of evidence that TH cells are essential for the terminal differentiation of G0 resting B cells in response to thymus-dependent antigens.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 3","pages":"155-67"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14111970","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":"Are xid B lymphocytes representative of any normal B cell population. A commentary.","authors":"D E Mosier","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 2","pages":"70"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14997049","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":"T cell receptor binding and unrestricted reactivity to GLT in somatic variants of an I-Ek specific T cell hybrid.","authors":"I A MacNeil,&nbsp;G K Sim,&nbsp;A A Augustin","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>T helper cell responsiveness to some synthetic polypeptides is controlled by Ir genes. It has been suggested that the inability of class II complexes to associate with conventional soluble antigens, on the surface of antigen presenting cells, can result in a characteristic pattern of antigen-specific T cell unresponsiveness, mapping to the I region of the MHC. Alternatively, during the establishment of self-tolerance, a hiatus could be generated in the T cell repertoire, when an epitope exhibited by a conventional antigen topochemically resembled (per se or in association with a self MHC epitope) a potentially immunogenic self antigenic determinant. The synthetic polypeptide GLT offers an interesting possibility for investigating the connection between tolerance to self-MHC antigens and Ir gene controlled unresponsiveness. It has been shown that mice which do not express I-Ek possess significant numbers of T cells which aberrantly recognize GLT in the context of various allogeneic class II MHC molecules. Moreover, if T cell populations obtained from such mice are depleted of alloreactivity to I-Ek in vitro, it results in the deletion of T cell clones specific for GLT presented by several I-A and I-E molecules. These observations are compatible with the hypothesis that GLT alone can mimic an I-Ek epitope, thus being able to interact directly with some of the T-cell receptors specific for I-Ek. Experiments presented in this communication indicate that GLT specifically inhibits the proliferation in vitro of a fraction of the MLR blasts generated against I-Ek. In addition, we characterize a T cell hybrid clone specific for I-Ek which can be functionally modulated by GLT.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 2","pages":"71-9"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13620684","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}