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

{"title":"Human anti-idiotypic T lymphocyte clones are activated by autologous anti-rabies virus antibodies presented in association with HLA-DQ molecules.","authors":"F UytdeHaag,&nbsp;I Claassen,&nbsp;H Bunschoten,&nbsp;H Loggen,&nbsp;T Ottenhoff,&nbsp;V Teeuwsen,&nbsp;A Osterhaus","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The regulatory function of antigen-specific T cells in human antibody responses to protein and carbohydrate determinants of many viral and bacterial antigens has extensively been studied in systems involving in vitro triggering of B cells by antigens or polyclonal activators. Although amply documented in experimental murine models, the existence of T helper cells with receptor specificity for idiotypic determinants of B cell immunoglobulins has not been demonstrated in a human system. We are interested in T helper cell recognition of idiotypic determinants of virus-specific antibody, secreted by human B cells in response to viral antigens, and in the role which such idiotype-specific T helper cells play, alone or in concert with virus-specific T helper cells, to regulate the antibody response. Understanding of the function of different T helper cell subsets in an anti-viral antibody response and especially of the mechanisms of idiotype recognition by T cells is important for the development, and future application in man of idiotype vaccines, the potential of which has been indicated for different pathogens in several animal species. It was realized that for the efficient characterization of each of the T helper cell subsets, the availability of cloned populations of T cells would be inevitable. Furthermore, we argued that if, as predicted by Jerne, idiotype recognizing T helper cells are involved in physiological idiotype regulation in the course of an immune response--e.g., following encounter with virus--cloned populations of T cells should best be obtained by immunization protocols closely mimicking the physiological situation. In a previous report we described the induction of a secondary antibody response in human peripheral blood mononuclear cells (PBMC) in vitro by rabies virus antigen. This response was shown to be T helper cell dependent, and rabies virus-specific T helper cell clones have recently been obtained in our laboratory. The present study describes the generation of cloned lines of anti-idiotypic T4+ cells from rabies virus immune PBMC restimulated with rabies virus antigen in vitro. The cloned T cell lines were found to respond to circulating autologous antibody exhibiting specificity to rabies virus, but not to rabies virus antigen. The clonal proliferation, induced by this \"auto-anticlonotypic\" antibody, was found to be preceded by modulation of the T3/Ti molecular complex and required presentation of the antibodies by antigen presenting cells in association with HLA-DQ molecules. This observation of MHC-restricted idiotype recognition by human T cells, may have important consequences for the understanding of the regulation of th</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"3 3","pages":"145-55"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14043470","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 the murine L3T4 molecule in T cell activation: differential effects of anti-L3T4 on activation by monoclonal anti-receptor antibodies.","authors":"C A Janeway,&nbsp;S Haque,&nbsp;L A Smith,&nbsp;K Saizawa","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>MHC restricted T cells can be divided into two subsets based on the mutually exclusive expression of the cell surface differentiation antigens L3T4 and Lyt-2 in the mouse. Expression of the L3T4 marker is correlated most strictly with recognition of foreign antigen in association with self class II MHC molecules, or Ia molecules. Less stringently correlated with L3T4 expression is the recognition of unmodified self or non-self Ia molecules. Finally, expression of L3T4 is also correlated with certain functional properties, although this correlation is even less stringent. The major correlation for function is between L3T4 and the ability to activate B cells. These correlations have led to the hypothesis that L3T4 recognizes Ia molecules, and plays a role in increasing the affinity of T cell:Ia bearing cell interactions. This hypothesis is bolstered by the finding that anti-L3T4 antibody blocks such interactions. Recently, we and others proposed a second effect of cross-linking L3T4 molecules, namely negative signalling. We further proposed that the natural ligand for L3T4 is Ia molecules, and that Ia-driven cross-linking of L3T4 molecules on the T cell in the absence of receptor aggregation would lead to off signalling to the T cell and separation of cell conjugates. To better understand the role of the L3T4 molecule in T cell activation, we have examined the effect of several anti-L3T4 antibodies on stimulation of a cloned line of helper T cells by a panel of monoclonal antibodies directed at what appear to be different epitopes on the T cell receptor. Unlike previous analyses of stimulation of helper T cells with anti-T cell receptor antibodies, we observe differential effects of anti-L3T4 on T cell activation by anti-receptor antibodies, the effect of anti-L3T4 depending on the characteristics of the anti-receptor antibody. This result suggests that L3T4 is intimately associated with the T cell receptor, and may thus play a critical role in T cell specificity as part of the antigen:Ia recognition complex. This proposed role is in keeping with the very strong correlation between L3T4 expression and recognition of self class II MHC molecules. While these studies do not provide definitive evidence for a physical association between L3T4 and the T cell receptor, they do place certain constraints on current models and suggest new possibilities for understanding T cell recognition and development.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"3 2","pages":"121-31"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14111812","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 origin of MHC-restriction of suppressor T cells--a commentary.","authors":"T Tada,&nbsp;Y Asano","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 4","pages":"232-3"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14111973","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":"Characterization of a hybridoma-derived T cell factor that promotes the production of antibodies bearing a dominant cross-reactive idiotype(s).","authors":"A M Wardzala,&nbsp;M B Bowen,&nbsp;G S Jendrisak,&nbsp;C J Bellone","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The participation of postulated subsets of T helper cells in antigen-specific antibody responses has generated both interest and controversy among immunologists. Specifically the import as well as the very existence of multiple populations of T helper cells has led to an intense search in recent years for cloned lines of such subsets that permit unambiguous classification and study. Furthermore, the means by which some of these T cells induce antibody responses may be via the elaboration of soluble factors mandating their characterization both biochemically and mechanistically. We have recently reported the existence of a T helper factor present in a 24-h Con A supernatant that specifically enhances an idiotype-bearing (Id+) response to trinitrophenol (TNP). The unique biochemical properties of this substance, namely, its capacity to bind both antigen and cross-reactive idiotype (CRI), has led to the generation of a cloned T cell hybridoma that constitutively \"secretes\" a factor which appears identical to the helper activity in Con A Sn. The cloned T cell hybridoma, herein designated LOP 1.4, elaborates a factor which selectively enhances the CRI+ anti-TNP antibody response in vitro. The specificity of the assay employed as well as its sensitivity for detecting significant enhancement of the percent CRI+ anti-TNP PFC response lent itself well as a useful vehicle for subsequent characterization of the factor. The LOP 1.4 factor, which can act at the later stages of the B cell response in a dose-dependent fashion, was characterized by affinity chromatography in order to probe the mechanism of its selective Id enhancement. The factor binds both the idiotype and the ligand for which one of the idiotype-bearing monoclonal antibodies is specific. That the factor binds idiotype and can be eluted selectively with ligand but not with noncross-reacting ligand suggests that the factor possesses separate but not independent binding sites, or alternatively, a single binding site that preferentially binds to a unique composite of antigen-idiotype. In addition, the factor bears I-J determinants, consistent with what we have previously detected on the surface of TH2-like cells. These results, collectively, suggest that the T cell hybridoma LOP 1.4 is a TH2-like cell (supporting the concept of multiple TH subsets) in light of its ability to enhance an idiotypic response to specific antigen through the production of a soluble factor that demonstrates affinity for both antigen and idiotype. In addition, like the I-J+ TH2 cell, the LOP 1.4 factor also bears I-J region determinants.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 5","pages":"243-53"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14111974","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":"Regulation of antibody production in vitro by granulocyte-macrophage colony stimulating factor.","authors":"K Grabstein,&nbsp;D Mochizuki,&nbsp;S Kronheim,&nbsp;V Price,&nbsp;D Cosman,&nbsp;D Urdal,&nbsp;S Gillis,&nbsp;P Conlon","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The precise molecular characteristics and the mode of action of the T cell derived lymphokines which augment antibody production in vitro remain uncertain. The use of ill-defined culture supernatants to dissect the cellular interactions in vitro involved in antibody production can lead to ambiguous results as the factors may act either on a contaminating non-B-lymphoid population or directly on the B lymphocyte. We report herein the development of a system for measuring in vitro primary antibody responses by murine spleen cells in which endogenous lymphokine production has been minimized by the in vivo administration of cytotoxic antibodies to deplete T lymphocytes and the addition of the glucocorticosteroid, dexamethasone, throughout the culture period. Using such an assay, a lymphokine activity was detected which was capable of augmenting the plaque forming cell response. This lymphokine was present in culture supernatant derived from the lectin activation of the T cell lymphoma, LBRM-33 and was distinct from other known B cell activators, notably IL-2 and IFN gamma. Biochemical purification of this activity indicated that it might be identical to granulocyte-macrophage colony stimulating factor (GM-CSF). The use of recombinant-derived GM-CSF protein unambiguously showed the role of this lymphokine in antibody production. These experiments demonstrated for the first time, the involvement of a hematopoietic factor in antigen-specific immune responses. Moreover, these results demonstrated an important regulatory circuit in the generation of antibody producing B cells in which GM-CSF, derived from activated T cells, stimulates macrophage function.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 4","pages":"199-207"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14462415","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 syngeneic T-T lymphocyte reaction (STTLR). II. Induction of primary T anti-T cell cytotoxic responses in vitro in T cell cultures stimulated with syngeneic self-reactive T cells.","authors":"H Suzuki,&nbsp;J Quintáns","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the previous paper in this series, we described a form of self-reactivity among T cells called the \"syngeneic T-T lymphocyte reaction\" (STTLR). The phenomenon involves responder T cells that are stimulated to proliferate by irradiated antigen or self-reactive cloned T cell lines. The proliferative STTLR occurs in cultures rigorously depleted of conventional APC and is inhibitable by anti-Ia antibodies of the appropriate specificity. We also showed that both L3T4+ Lyt2- and L3T4- Lyt2+ T cell subsets participate in the STTLR-induced by the IEk-specific Lbd T cell line. In this paper, we report our studies on the effector phase of STTLRs, in particular, the cytotoxic responses induced by Lbd cells. We demonstrate that uncloned and cloned lines (called Dbl) of anti-Lbd cytotoxic cells are L3T4- Lyt2+ effector cells that kill Lbd, antigen-reactive T cells, and syngeneic B cells stimulated with LPS. They also kill syngeneic splenic cells stimulated with Con A for 72 h or less; longer culture periods in the presence of Con A yield Dbl-resistant T cells. Resting T cells are also resistant to Dbl cells. Using LPS-induced splenic B cells from H-2 congenic mice, we map the anti-self specificity of uncloned and cloned anti-Lbd cells to the Kk + IAk regions of the MHC. Seemingly concordant results were obtained using L transformants expressing IAk molecules on their surface. However, control studies with fibroblast lines and UV-induced fibrosarcoma cells unexpectedly revealed a high susceptibility to lysis by Dbl cells among certain Ia- cell lines. These results suggested that the antigen recognized by Dbl cells is not IAk itself but either an MHC-encoded or MHC-regulated gene product expressed by activated T and B cells and certain tumor cells. The target antigen is important in immunoregulation because Dbl cells suppress both the proliferation of Lbd cells to syngeneic cells and primary T cell-dependent anti-SRC PFC responses. From an immunoregulatory viewpoint, the existence of Lbd-Dbl cells offers several appealing features. Since Lbd cells cannot activate resting B cells or replace antigen-specific helper cells, they cannot initiate immune responses nonspecifically. In the presence of the appropriate antigen-specific helper T cells, Lbd and other self-reactive cells can amplify an immune response and thus facilitate its exponential growth. Since the self-reactive cells activate the Dbl cytotoxic circuit described above, they also provide the stimulus required to terminate immune responses quickly.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 6","pages":"345-57"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14634019","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 lymphocytes from irradiation chimeras repopulated with 13-day fetal liver cells recognize antigens only in association with self-MHC products.","authors":"E Nisbet-Brown,&nbsp;E Diener","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The restriction specificities of maturing thymocytes are determined by the Class II MHC antigens expressed by non-lymphoid thymic tissues. The proliferative response of mature T lymphocytes to antigen-presenting cells (APC) and antigen requires that the APC express the same MHC antigens as the thymus in which the T cells differentiated. Thus, in the two-way bone marrow chimera [A + B----(A x B)F1], T lymphocyte populations of A and B haplotypes have each acquired the potential to recognize antigens associated with either parental haplotype. In spite of the large body of work on MHC restriction, we still do not have a clear understanding of the mechanisms which impose self restriction. The chimeric model systems used previously to study MHC restriction have used adult bone marrow cells as the source of lymphoid precursors. During normal ontogeny, T cells are derived from precursors in the fetal liver and we felt that a direct comparison of T cells from fetal liver and bone marrow-repopulated animals would shed light on the development of MHC restriction specificities during T cell ontogeny in the thymus or prethymically. We found that parental T lymphocyte populations isolated from two-way fetal liver chimeras cooperated only with syngeneic APC, while those from bone marrow chimeras cooperated with APC of either parental haplotype. This suggests that fetal liver and bone marrow may not be equivalent sources of stem cells. Our results may be due to fundamental differences between thymocyte precursors in fetal liver and bone marrow, including the time course of their expression of T cell receptor gene products.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 4","pages":"235-42"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14044311","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":"A cloned T cell line that selectively augments antibody responses of phosphorylcholine-specific B cells bearing the T15 idiotype.","authors":"E B Dunn,&nbsp;J Kim,&nbsp;K Bottomly","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Helper T (Th) cells have shown to be heterogeneous both in their function and in their specificity. Several studies have demonstrated that there exist Th cells which do not appear to be specific for antigen:Ia complexes (not H-2 restricted) but interact with the target B cell via recognition of immunoglobulin idiotypic determinants. In analyzing anti-phosphorylcholine (PC) responses, such idiotype-specific Th cells are characterized by 1) their ability to increase responses to phosphorylcholine by augmenting selectively the activation of T15-idiotype-bearing PC-specific B cells, 2) their ability to bind specifically to T15-bearing immunoglobulin and 3) the dependence of their maturation on circulating T15 idiotype rather than Ia. Our aim is to explore further the relationship between Ia-specific and T15-specific Th cells. These studies describe the first step in comparing specificity and function of idiotype-specific Th cells to other known Th cells by the cloning of a T15-specific Lyl T cell (ThId) with properties consistent with those described for uncloned populations. The cloned ThId cells generated do not activate B cells to secrete antibody but augment anti-PC plaque forming cell (PFC) responses induced by Ia-restricted Th cells. This augmentation is seen only in the T15-bearing PFC responses even though non-T15-bearing B cells are equally accessible, and it is seen only in PC responses and not responses to TNP under identical culture conditions.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 4","pages":"209-17"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14111972","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":"H-2-linked Ir gene control of VH determinant(s)-specific helper T cells.","authors":"D J Kawahara,&nbsp;P Marrack,&nbsp;J W Kappler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The fact that helper T cells (Th) recognize antigen in the context of class II MHC antigens is well documented. T cells specific for immunoglobulin (Ig) determinants have been demonstrated as have Th cells that interact with B cells in an idiotype (Id)-restricted manner. It is still controversial whether or not such T cells recognize idiotype in an MHC-restricted fashion. In tackling this problem it is important to have a T cell population selected by the introduction of the Ig bearing the determinant(s) in question and to have both the T cell and B cell populations unbiased by prior intentional exposure to specific exogenous antigen. Thus, the likelihood of such specific antigen-induced interactions is reduced and a clearer view of the Ig-induced interaction can be obtained. With this in mind, we found that T cells from B10.D2 mice immunized with normal BALB/c serum Ig were able to stimulate the response of BALB/c B cells to sheep red blood cells (SRBC) in vitro. H-2-linked Ir gene control was revealed by the ability of these Th cells to recognize BALB/c Ig in association with H-2d (BALB/c) but not H-2b (BALB.B). Through the use of Igh congenic mice, BAB/14 and C.B20, we found the Th cells to be specific for VH (idiotypic) rather than CH (allotypic) determinants; the determinant(s) in question was apparently expressed on some BALB/c anti-SRBC antibodies since these Th cells could help anti-SRBC responses but not anti-horse or anti-burro RBC responses. This conclusion of idiotypic specificity was supported by the fact that these Th cells could be primed with either IgM or IgG from BALB/c serum, one BALB/c anti-SRBC hybridoma protein but not two others or a BALB/c IgM myeloma protein, and by the fact that absorption of the serum on SRBC prior to separation of the Ig for immunization removed the priming ability of that Ig preparation. From the use of B cell mixing experiments, it was determined that the restriction elements of H-2 complex and the appropriate Ig determinants had to be borne on the responding B cells, suggesting that direct T-B collaboration was involved in the Th cell action. Therefore, by priming with normal serum Ig we have generated Th cells which act through direct interaction with responding B cells via a VH determinant(s). In addition, unlike the findings of others using different methods of priming Id-specific Th cells, these Th cells are under H-2-linked Ir gene control.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 5","pages":"255-64"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14111975","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":"Antigen presentation by astrocytes--a commentary.","authors":"L A Levin,&nbsp;H L Weiner","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 5","pages":"281-2"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14281072","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}