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

{"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":"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}

{"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":"Immunoregulatory pathways in adult responder mice. III. Establishment of a GAT-specific suppressor T cell clone from GAT-tolerant responders which afferently regulates DTH responses.","authors":"M K Jenkins,&nbsp;S D Miller","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Recent advances in the biochemical and genetic analysis of soluble immunoregulatory molecules (TsF) have been achieved via the establishment of cloned TsF-producing T cell hybridomas. However, studies on in vivo regulation of immune responses have been hampered by the lack of clonal populations of nontransformed suppressor T cells (Ts). Nonhybridoma Ts clones would allow cellular dissection of complex Ts circuits and precise analyses of Ts effector mechanisms. Our laboratory has recently demonstrated that poly(Glu60Ala30Tyr10) (GAT)-specific unresponsiveness is induced in adult responder mice tolerized via the intravenous injection of GAT-coupled syngeneic spleen cells (GAT-SP). This unresponsiveness is mediated by two antigen-specific mechanisms--nontransferable clone inhibition and induction of transferable Ts which regulate both humoral and T cell-mediated delayed-type hypersensitivity (DTH) responses. We have thus applied methodology used for the production and maintenance of antigen-specific T helper (Th) clones in an attempt to establish and characterize Ts clones mediating GAT-specific in vivo suppressive activity. Therefore, spleen cells from GAT-SP tolerant responder mice were maintained in continuous culture with soluble GAT, 10% concanavalin A-conditioned medium (IL-2), and irradiated syngeneic antigen presenting cells (APC). A stable, long-term Ts cell line (J372) was isolated by this procedure. This line and one of its clones (J372.2) suppressed the afferent (induction), but not efferent (elicitation) phase of GAT-specific DTH. In contrast, the J372.2 Ts clone had no inhibitory effect on the development of specific T cell proliferative responses. Intravenous injection of small numbers (2-5 x 10(6)) of J372.2 Ts cells resulted in significant suppression of DTH responses in GAT-primed, but not in ovalbumin- or methylated bovine serum albumin-primed recipients, demonstrating the antigen-specificity of the suppression. Intravenous injection of a GAT-specific Th clone (JTL-E1) or of a DNP-specific Th line (JTL-DNP) had no suppressive effects on GAT-specific responses suggesting that J372.2-mediated unresponsiveness is the result of active suppression, and not the result of nonspecific inhibitory effects of activated T cells. More importantly, normal GAT-specific DTH responses in recipients of the JTL-E1 Th clone (maintained in the same GAT concentration as J372.2) indicated that J372.2-mediated suppression was not due to induction of nontransferable tolerance by surface-associated GAT.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 1","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14112071","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":"Cloned Lyt-1+, 2- T suppressor cells--a commentary.","authors":"R J Hodes","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 1","pages":"14-6"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14112072","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 development in B cell deficient mice. III. Restriction specificity of suppressor T cell factor(s) produced in mice treated chronically with rabbit anti-mouse mu chain antibody.","authors":"K T HayGlass,&nbsp;S J Naides,&nbsp;B Benacerraf,&nbsp;M S Sy","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A role for Igh linked genes and the idiotypes they encode has been implicated in the activity of a variety of T cell subpopulations. Idiotype restricted T cell function has been observed for helper and suppressor cell populations. The finding that T cell receptor genes are distinct from B cell receptor (Igh) genes strongly argues against a direct role for immunoglobulin genes in the determination of the T cell repertoire. Nevertheless, idiotypic Ig determinants may play an indirect role in influencing the ultimate composition of the T cell repertoire. One approach to this question involves evaluation of T cell activity upon development in an immunoglobulin deficient environment. The availability of antigens which elicit T cell and antibody responses characterized by the expression of dominant crossreactive idiotypes under the control of Igh genes provides an ideal approach to investigate the basis for the expression of Igh-like structures on T cells and the concomitant functional genetic restrictions they determine. Thus, we have prepared B cell deficient mice by continuous treatment, beginning at birth, with rabbit anti-mouse IgM. The network which comprises the suppressor T cell response to azobenzenearsonate (ABA) was then examined in normal and anti-mu treated mice to assess what role, if any, immunoglobulin encoded determinants play in influencing the composition of the peripheral T cell pool. The results clearly demonstrate that the absence of Ig+ B cells leads to major alterations in the composition of the T cell repertoire. Anti-mu treated, but not normal rabbit Ig treated, mice produce TsF1 which fails to suppress cytotoxic T lymphocyte or helper T cell responses of normal syngeneic mice, yet efficiently suppresses those of syngeneic anti-mu treated recipients. Reciprocally, normal TsF1, though suppressive in normal Igh-1 syngeneic recipients, fails to affect the development of responses in anti-mu treated syngeneic mice. TsF1 obtained from anti-mu treated mice is antigen-specific. Testing of anti-mu TsF in a variety of normal or anti-mu treated recipients reveals no MHC restrictions. In marked contrast, anti-mu TsF reflects a novel pattern of Igh functional restrictions. The observed Igh restrictions were found to map to the idiotype encoding VH regions of the Ig heavy chain gene cluster (Igh-VH). The results demonstrate that T cell maturation in the virtual absence of environmental immunoglobulin can lead to profound changes in the composition of the T cell compartment. The means by which the absence of Ig encoded determinants leads to such changes is speculated upon.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 2","pages":"107-17"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14112562","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":"Oncogene expression in autoimmune mice.","authors":"J D Mountz,&nbsp;J F Mushinski,&nbsp;G E Mark,&nbsp;A D Steinberg","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Systemic autoimmune disease states are known to be associated with abnormal cell growth or differentiation. In the murine models of systemic lupus erythematosus (SLE), specific genotypes result in dysregulated growth of certain lymphocyte subpopulations. Although genes underlying autoimmune syndromes have been characterized by mendelian genetics, it has not yet been possible to characterize them at the molecular level. Recently, it has become clear that cellular proto-oncogenes can regulate cell growth and differentiation. Therefore, we have studied the expression of five different proto-oncogenes; myc, myb, abl, bas, and raf, in organs and cells of various autoimmune strains. These genes were selected because each has previously been associated with abnormal hemopoietic cell growth, and because each has been at least partially characterized at the molecular and functional level. We have found selective abnormal proto-oncogene expression associated with the characteristic abnormal cell growth or differentiation of lymphocytes of autoimmune mice. The lymph nodes of MRL-lpr/lpr mice are packed with unusual T cells. These had a marked increase in myb expression. There was a 20-40-fold increase in myb RNA in lymph nodes of lpr/lpr mice on several different genetic backgrounds. The gld/gld mouse has a very similar unusual T cell in the lymph nodes: it also had a comparable increase in myb RNA in the nodes. In contrast, myb expression was not elevated in the other autoimmune mouse strains lacking these abnormal T cells. Whereas such lpr/lpr mice had increased myb expression in the lymph nodes and splenic T cells, they had markedly subnormal myb expression in the thymus, an organ with high myb in normal and in the other autoimmune strains. These results suggest that one phase of intrathymic differentiation in other mice occurs in the periphery of lpr/lpr mice. The spleens of NZB and male BXSB mice had increased myc expression which was found to be associated with B cells upon cell separation. Similarly, increased bas and abl expression was associated with autoimmune B cells. The xid gene, which retards or prevents the expression of murine lupus by retarding B cell maturation, was associated in BXSB.xid, NZB.xid, and MRL-lpr/lpr.xid congenic mice with marked reduction in expression of myc, bas, and abl in the spleens containing B cells, but not of myb in the lpr/lpr.xid nodes containing primarily the unusual T cells. Raf expression was found to be associated in lpr/lpr and gld/gld mice with both the unusual T cells and splenic B cells.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 3","pages":"121-31"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"15031972","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":"Interaction between genes of chromosome 12 and I-region genes in the control of the arsonate-specific T cell repertoire.","authors":"M Seman,&nbsp;E Trannoy,&nbsp;M F de Castaneda,&nbsp;D Regnier","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The T lymphocyte repertoire consists of clones recognizing foreign antigens together with self histocompatibility molecules. Diversification of the receptor is believed to arise by somatic mechanisms during ontogeny. MHC gene products are essential for this process as well as for antigen recognition and expression of T cell functions. Yet, the antigen-specific T cell receptor is not encoded by MHC genes. Little is still known concerning the nature and the genetic origin of this receptor despite numerous experimental approaches. Although the T cell repertoire is mainly determined, in a single individual, by the alleles expressed at the MHC locus, one can postulate that it could also be influenced by the existence of alleles of the germ line gene(s) encoding the T cell receptor. If so, an analysis of the T cell fine specificity in mice of the same H-2 haplotype with different background genes might permit the mapping of the genes coding for this receptor. Such an experimental approach requires the use of an antigen consisting of only one major determinant. Several recent observations suggested to us that the hapten p-azobenzenearsonate (ABA) was a suitable model for such investigations. Thus, we decided to compare the specific pattern of responses to ABA-tyrosine, ABA-histidine and to free ABA in different inbred mouse strains. We report here that the lymph node T cell proliferative response to these molecules is under the control of an ABA-specific Ir gene. The ABA-Tyr conjugate is the most potent immunogen of the three in vivo as well as in vitro. High responder strains to ABA-His or ABA are included in the group of high responders to ABA-Tyr suggesting that the response to the three molecules is under the control of the same Ir-gene. The pattern of the response is also influenced by background gene(s). One of these can be localized on chromosome 12 using congenic mice. No close linkage to IgCH markers or VH idiotypes can be demonstrated but a linkage of this gene(s) to the Pre-1 locus seems possible. B lymphocytes do not seem to account for the involvement of Chr.12-genes in the response since; in our experimental system, they do not present ABA to T cells nor do they proliferate in the assays. Similarly, ABA-Tyr-antibody complexes do not enhance macrophages presentation of ABA to T cells, which supports the conclusion that IgCH or VH gene products are not involved in the control of the response.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"1 4","pages":"223-35"},"PeriodicalIF":0.0,"publicationDate":"1984-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17502545","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":"Helper functions of antigen-induced specific and autoreactive T cell colonies.","authors":"M Zauderer,&nbsp;H Campbell,&nbsp;D R Johnson,&nbsp;M Seman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Helper T cells have been distinguished on the basis of whether they provide carrier-specific or nonspecific helper functions. In previous experiments we determined that the predominant class of helper T cell in populations of primed lymph node cells is a nonspecific helper T cell unable to provide carrier-specific signals. Initial induction of nonspecific helper T cells in vitro requires restimulation with the immunogen. This suggested that such T cells may express antigen-specific receptors. In this case they would constitute a unique subpopulation distinct from T cells with identical antigen-specificity that are able to provide carrier-specific help. Alternatively, the requirement for antigen restimulation might reflect a role for antigen-specific T cells in the recruitment of T cells with unrelated specificity. To distinguish between these possibilities we have characterized the specificity and function of helper T cell colonies selected from primed lymph node cells. We report here isolation of autoreactive as well as antigen-specific helper T cells. All antigen-specific T cell colonies provide carrier-specific help in the presence of the homologous hapten-carrier conjugate. Only autoreactive T cells are limited to providing nonspecific helper function. Although selection of autoreactive T cells is initially dependent on antigen restimulation in vitro, activation of an established autoreactive T cell line requires restimulation with MHC-syngeneic spleen cells but does not require restimulation with either the immunogen or fetal calf serum. These results suggest that nonspecific helper T cells induced in the course of a normal immune response to randomly chosen foreign antigens are autoreactive. Such T cells may serve to enhance proliferation and maturation to immunoglobulin secretion of B cells activated by limiting numbers of carrier-specific helper T cells. The demonstration of large numbers of precursors to MHC-specific autoreactive T cells in antigen-primed populations raises important issues concerning regulation of the expansion of autoreactive T cells in vivo.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"1 2","pages":"65-77"},"PeriodicalIF":0.0,"publicationDate":"1984-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17306951","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 IgE antibody system: mature, peripheral B lymphocytes exert regulatory influences on the IgE systems of self-reconstituting, sublethally irradiated mice.","authors":"D H Katz,&nbsp;C A Bogowitz,&nbsp;L R Katz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Previous studies have documented clear biological differences, such as sensitivity to moderate doses of irradiation, between B lymphocytes of the IgE type and B lymphocytes of other immunoglobulin isotypes. The present experiments were originally designed to explore such differences further by comparing the abilities of B lymphocytes derived from various IgE responder phenotypes, which differ among various inbred mouse strains, to reconstitute in a positive way the ability of sublethally irradiated recipient mice (of syngeneic or semisyngeneic type) to mount specific immune responses of the IgE antibody class. This was an important question with regard to delineating fully underlying differences in IgE responder phenotypes among different mouse strains, since heretofore most of the emphasis in experimentally defining such differences has focused on differences in T cell function, rather than B cell function. The experimental approach chosen to address this question seemed logical for two reasons: 1) it was our expectation that following exposure to the dose of irradiation employed (700 rads), individual mice would only slowly repopulate peripheral lymphoid tissues with their own stem cell products, and hence the expression of IgE responsiveness observed could be expected to reflect the responsiveness of the donor B cell population transferred into such recipients; and 2) since recipient mice were carrier-primed one week prior to irradiation in order to create a pool of radioresistant carrier-specific helper T cells, one could expect that this amplified pool of helper T cells would hasten the development of antibody production by the transferred donor B cells.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"1 2","pages":"83-9"},"PeriodicalIF":0.0,"publicationDate":"1984-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17306952","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}