bluuebunny/crossref_metadata_2025_split huggingface dataset:
The variable occurrence of CD45RA on CD8+ thymocytes correlates with the presence of Mtv sequences; its expression on other thymocytes is rare
Authors: Huby Russell D. J. , Goff Lindsey K. 
Published: March 2007

AbstractWhile all thymocytes express CD45, only a small fraction (<3% in mice) bear the high molecular weight isoform, CD45RA. It has been suggested that these cells alone constitute the generative thymocyte lineage and should, therefore, occur within every ontogenic subset. To test this, we determined CD45RA expression among thymocyte subsets defined by CD4 and CD8. In some strains, exemplified by C57BL/Icrf, very few (< 0.2%) Tthymocytes expressed CD45RA and were mostly CD4−CD8− or CD4+CD8+, inconsistent with them constituting the generativelineage. In others, exemplified by BALB/c, CD45RA was expressed on up to 3% of T thymocytes, which were mostly CD4−CD8+. The limited occurrence of CD4−CD8+CD45RA+ thymocytes suggests that they are a nonconstitutive subset playing a role in the thymus of only some strains. Their occurrence correlates with that of Mtv proviruses within the mouse genome; however, their T cell receptor Vβ repertoire is diverse, suggesting they are not uniquely selected by Mtv superantigens. We propose that they may be mature CD8 T cells, possibly responsible for introducing viral superantigens into the thymus.
High frequency of cord blood lymphocytes against mycobacterial 65‐kDa heat‐shock protein
Authors: Fischer Heinrich Peter , Sharrock Claire E. M. , Panayi Gabriel S. 
Published: March 2007

AbstractA high frequency of nonadherent mononuclear cells in human cord blood proliferates in response to mycobacterial 65‐kDa heat‐shock protein. The frequency range in cord blood is not different from that in peripheral blood of Bacillus Calmette‐Guérin vaccinated adults. In comparison we found 10 to 100 times lower frequencies to purified protein derivative in nonadherent cord blood mononuclear cells thanin adult peripheral blood mononuclear cells. These findings may provide experimental support for Cohen's theory of the immunological homonculus.
Anti‐arthritic effects demonstrated by an interleukin‐2 receptor‐targeted cytotoxin (DAB486IL‐2) in rat adjuvant arthritis
Authors: Bacha Patricia , Forte Serene E. , Perper Stuart J. , Trentham David E. , Nichols Jean C. 
Published: March 2007

AbstractDAB486IL‐2 is an interleukin‐2 receptor‐specific cytotoxin which selectively targets and kills cells which bear the high‐affinity form of the IL‐2 receptor. Since elimination of activated T lymphocytes may be useful in the treatment of rheumatoid arthritis, the effect of DAB486IL‐2 treatment in an animal model of arthritis was investigated. We demonstrated that rats treated with DAB486IL‐2 during the induction phase of disease have delayed onset of symptoms and significantly reduced severity of inflammation as well as a depressed proliferative response to mycobacterial stimulation in vitro. In addition, the presence of preexisting antibodies to the molecule had no impact on the anti‐arthritic effects observed in this model. These data suggest that DAB486IL‐2 may have therapeutic potential in the treatment of rheumatoid arthritis.
Minimal growth requirements of mature T lymphocytes: interleukin (IL)‐1 and IL‐6 increase growth rate but not plating efficiency of CD4 cells stimulated with anti‐CD3 and IL‐2
Authors: Soldaini Elisabetta , Robson MacDonald H. , Nabholz Markus 
Published: March 2007

AbstractWe show that interleukin (IL)‐2 is necessary and sufficient for the proliferation of both CD4 and CD8 subsets of peripheral murine T cells activated by plastic‐bound anti‐CD3 monoclonal antibodies (mAb). The frequency of proliferating cells (f) was 0.32 for CD4 cells and 0.63 for CD8 cells. These frequencies were not increased by the addition of IL‐1 or IL‐6, alone or in combination. These cytokines were unable to induce responsiveness to IL‐2 in T cells confirming that they cannot substitute for the signal delivered via the TcR/CD3 complex. On the other hand, IL‐1 and IL‐6 increase the growth rate of CD4 cells. The addition of IL‐6 significantly lowered the mean doubling time (dt) of CD4 cells (dt: 26 h vs. 38 h in the presence of IL‐2 alone, p < 0.01), while the addition of IL‐1, ineffective by itself, combined with IL‐6 further increased the growth rate of CD4 cells (dt: 23 h, p < 0.001). The growth rate of CD8 cells stimulated with anti‐CD3 and IL‐2, was markedly faster than that of CD4 cells (dt: 18 h vs. 38 h, p < 0.001) and was not significantly influenced by addition of IL‐1 and/or IL‐6.
Genetic control of nonresponsiveness to hepatitis B virus vaccine by an extended HLA haplotype
Authors: Hatae Ken , Kimura Akinori , Okubo Ryoko , Nishimura Yasuharu , Sasazuki Takehiko , Watanabe Hiroshi , Erlich Henry A. , Ueda Kohji 
Published: March 2007

AbstractWe previously reported evidence for a statistical association between the serologically determined HLA‐Bw54, DR4 and DRw53 alleles and the non‐immune responsiveness to hepatitis B virus surface antigen (HBsAg) in the Japanese population. To identify the locus and allele within the HLA region associated with the nonresponsiveness to HBsAg, serological HLA typing, DNA typing of HLA‐DQ and DP alleles using amplified HLA genes and sequence‐specific oligonucleotide probes, and restriction fragment length polymorphism (RFLP) analysis of the fourth component of complement (C4) genes were performed in healthy unrelated Japanese vaccinees who were immunized subcutaneously three times with plasma‐derived HBsAg vaccine. In nonresponders to HBsAg, the frequencies of HLA‐Bw54 cross‐reactive epitope group (CREG); (Bw54, Bw55, Bw56 and other Bw22), C4 RFLP (6.5 kb + 12.0 kb), DR4, DRw53 and DQw4 (DQA1*0301‐DQB1*0401) were increased and the frequencies of HLA‐DR1, DRw6 and DQw1 were decreased as compared with those in healthy unrelated controls. Further analysis revealed that the coexistence of HLA‐Bw54CREG and DR4‐DRw53‐DQw4 (DQA1*0301‐DQB1*0401) was associated with the nonresponder group, whereas, donors positive for exclusively either Bw54 CREG or DR4‐DRw53‐DQw4 (DQA1*0301‐DQB1*0401) were not associated with the nonresponder group. Because there is a strong linkage disequilibrium between HLA‐Bw54CREG, C4 RFLP (6.5 kb + 12.0 kb) and HLA‐DR4‐DRw53‐DQw4 (DQA1*0301‐DQB1*0401) in the Japanese population, the extended HLA‐Bw54CREG‐C4 RFLP (6.5 kb + 12.0 kb)‐DR4‐DRw53‐DQw4 (DQA1*0301‐DQB1*0401) haplotype may well control nonimmune responsiveness to HBsAg. This extended HLA haplotype controls nonresponsiveness as a dominant genetic trait because all ten heterozygotes and two of three probable homozygotes of this extended HLA haplotype were nonresponders.
Enhanced expression of tumor necrosis factor receptor mRNA and protein in mononuclear cells isolated from rheumatoid arthritis synovial joints
Authors: Brennan Fionula M. , Gibbons Deena L. , Cope Andrew P. , Feldmann Marc , Mitchell Tracey , Maini Ravinder N. 
Published: March 2007

AbstractWe previously proposed the hypothesis that the pro‐inflammatory cytokine tumor necrosis factor‐α (TNF‐α) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA) based on our observations that it is the dominant inducer of interleukin‐1 (IL‐1) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) production in RA synovial joint mononuclear (MNC) cells in culture. Since TNF‐α acts via two membrane receptors, we have extended those studies to investigate the distribution of the p55 and p75 TNF receptors (TNF‐R) in RA tissue. Surface receptor expression was quantitated by flow cytometry using monoclonal antibodies specific to the p55 (HTR‐9) and the p75 (UTR‐1) TNF‐R. Both receptors were significantly increased on MNC isolated from the synovial membrane of RA patients compared to normal or RA peripheral blood MNC. Interestingly, the p75 TNF‐R was increased both on large monocytic/macrophage‐type cells and CD3+ lymphocytes. Furthermore, there was a significant increase in the proportion of CD3+ cells in RA synovial fluid expressing the p75 TNF‐R, compared to matched peripheral blood MNC. In contrast to RA synovial MNC, p75 or p55 TNF‐R expression was not significantly increased in osteoar‐thritis synovial MNC. In addition, Northern blot analysis indicated abundant expression of both p55 and p75 mRNA in RA synovial joint MNC. This was in contrast to normal peripheral blood MNC cells which contained little or no constitutive TNF‐R mRNA; following stimulation with phytohemagglutinin and IL‐2, a rapid and transient expression of both receptor mRNA was induced. These results, therefore, indicate that in RA synovial joint tissue there is up‐regulation of both p55 and p75 TNF‐R mRNA and surface protein expression, and with the presence of TNF‐α in RA tissues, these results provide support to our hypothesis that TNF‐α is of critical importance in the pathogenesis of RA.
The use of a non‐depleting anti‐CD4 monoclonal antibody to re‐establish tolerance to β cells in NOD mice
Authors: Hutchings Patricia , Reilly Lorraine O' , Parish Nicole M. , Waldmann Herman , Cooke Anne 
Published: March 2007

AbstractThe use of immunosuppressive drugs in the management of autoimmunity penalizes a large part of the immune system for the misdemeanors of a small minority of T cells. An ideal form of therapy would be one in which it were possible to render the immune system tolerant of the inciting antigens with minimal effects on other responses. We here show that it is possible to re‐establish self tolerance in an animal model of insulin‐dependent diabetes mellitus without prior deletion of CD4+ T cells using a short course of therapy with a non‐lytic monoclonal antibody to the CD4 adhesion receptor on T cells. This tolerance can be achieved even when diabetogenic cells are already in the pancreas. Primary responses to antigens given after therapy has ceased are normal and secondary responses to antigens seen prior to, but not during, the period of antibody therapy can remain unaffected. This suggests that intervention with selected CD4 antibodies may have significant advantages over and above that provided not only by conventional immunosuppression but also over that provided by a depleting antibody.
In vivo responses of CD4+ and CD8+ cells to bacterial superantigens
Authors: Herrmann Thomas , Lees Rosemary K. , Robson MacDonald H. , Baschieri Selene 
Published: March 2007

AbstractStaphylococcal enterotoxin B (SEB) is a bacterial superantigen that binds to major histocompatibility complex (MHC) class II molecules and specifically activates T cells bearing Vβ8 T cell receptor domains. We have compared several aspects of the response of CD4+ and CD8+ T cell subsets to SEB in vivo. Vβ8+ cells in both subsets proliferated to a similar extent upon SEB injection. Furthermore, mRNA for interferon‐γ was induced in both subsets with similar kinetics and SEB dose‐response. Finally CD8+ (but not CD4+) T cells from SEB‐injected mice exhibited SEB‐specific lysis of MHC class II‐bearing target cells. Collectively, these data indicate that the CD4:MHC class II interaction confers no detectable selective advantage to CD4+ cells in the in vivo response to SEB. The observed effector functions of both subsets may contribute to SEB‐induced immunopathology.
Bone marrow cells of athymic nude mice express functional T cell receptor α chain transcripts rearranged to Vδ2, 3, 4, 5, 6 genes
Authors: Spieß Sibylle , Kuhröber Andreas , Schirmbeck Reinhold , Reimann Jörg 
Published: March 2007

AbstractFrom bone marrow cells (BMC) of athymic nude mice, T cell receptor (TcR) α chain transcripts were selectively amplified by polymerase chain reaction (PCR) using Vδ2−, Vδ3−, Vδ4−, Vδ5−, Vδ6− and Cα‐specific primers. Amplified DNA fragments were cloned, and 32 randomly selected clones from 5 PCR were sequenced. Twenty‐three distinct rearrangement events were detected, of which 87% (20/23) were in‐frame. All five tested Vδ genes (Vδ2, 3, 4, 5, 6) rearranged in‐frame to Jα−Cα. N‐region diversity in Vδ−Jα junctions present in most clones was limited to two to five nucleotides. P‐nucleotide additions in this region were also detected. The Vδ5 gene located 3′ of Cδ in reversed transcriptional orientation was rearranged to Jα by inversion. The Jα usage pattern of the sequenced clones was strongly biased towards rearrangement of the most 5' genes (located nearest to Cδ) of the Jα cluster: the most 5′ Jα (Jα TA1) was used by 30% of all clones, and 78% of all Jα rearranged to Vδ were located in the 5′ 12 kb of the 60‐kb Jα cluster. As distinct Vδ/Cδ and Vα/Cα TcR usage patterns are prevalent in peripheral T cell populations, our data suggest that these TcR usage patterns results from repertoire selections operating in αβ and γδ T cell lineages, but not from preferential Vδ‐Cδ and Vα‐Cα rearrangement patterns.
Regulation of graft‐versus‐host‐reaction by Mlsa‐reactive donor T cells
Authors: Muluk Satish C. , Hakim Frances T. , Shearer Gene M. 
Published: March 2007

AbstractInjection of A/J splenocytes (H‐2Dd, Mlsc) into unirradiated (A/J x CBA)F1 (BAF1) host mice (H‐2Dd/k, Mlsd) results in an acute suppressive graft‐vs. ‐host reaction (GVHR), characterized by immune dysfunction and appreciable donor cell engraftment; injection of the CBA/J parent (H‐2Dk, Mlsd), which recognizes no Mls disparity in the host, results in little or no GVHR. Furthermore, the Mlsa‐reactive Vβ6 and Vβ8.1 T cell subsets in A/J T cells expand significantly in the GVHR host. Finally, depletion of Vβ6+ and Vβ8.1+ from the A/J population abrogates the proliferative response to BAF1 in vitro and the development of GVHR in vivo. Thus, the response to Mls determinants can contribute to the generation of a GVHR.
Induction of antigen‐specific tolerance by cyclosporin A
Authors: Stitz Lothar 
Published: March 2007

AbstractRecently, we reported preliminary evidence for the induction of tolerance in vivo by cyclosporin A (CSA) during a persistent virus infection in rats. In the present communication, those observations are verified and the findings extended to the functional level of cell‐mediated immunity. Mice infected intracerebrally with lymphocytic choriomeningitis virus (LCMV) normally die from a fatal immunemediated disease after 6–8 days but they do not succumb if treated intraperitoneally with 50 mg/kg/day of CSA. Immunosuppression initiated one day before infection and continued for at least two consecutive weeks resulted in the absence of immunopathologic disease of the brain and in the survival of mice, which were found to be persistently infected virus carriers. In these animals, no cytotoxic T cell activity could be detected. The effect of CSA was not due to a toxic effect on the immune response since immune reactivity was restored as early as 4 days after discontinuation of the drug in control animals. Neither secondary in vitro nor in vivo restimulation resulted in the generation of a cellular antiviral immune response. Cytotoxic T cell reactivity to third‐party antigen, however, could be detected, although somewhat delayed. Additionally, spleen cells from CSA‐treated mice did not clear the virus from LCMV‐infected recipients upon adoptive transfer, whereas spleen cells from LCMV immune mice completely eliminated virus infection in carrier mice. However, mice immunosuppressed with CSA and infected with vesicular stomatitis virus (VSV) did not generate a primary immune response but were immunologically fully reactive to challenge infection, providing evidence for the absence of tolerance and the presence of antigen‐specific temporal unresponsiveness. Thus, as exemplified by VSV infection in which the virus does not replicate to considerable titers in mice and viral antigens do not persist, the presence of the foreign antigen for prolonged periods of time could be shown to be a conditio sine qua non for CSA‐induced tolerance.
Presentation of superantigen by human T cell clones: A model of T‐T cell interaction
Authors: Nisini Roberto , Matricardi Paolo M. , Fattorossi Andrea , Biselli Roberto , D'amelio Raffaele 
Published: March 2007

AbstractSuperantigens (SAg) interact with T lymphocytes bearing particular Vβ sequences as part of their T cell receptor (TcR). The interaction, however, requires the presence of major histocompatibility complex (MHC) class II molecules on antigen‐presenting cell (APC). In peculiar circumstances, MHC class II+ T cell clones (TCC) have been shown to present peptides and selected antigens interacting with antigen‐specific TCC in the absence of APC. In this report we studied the capacity of SAg to mediate a T‐T cell interaction, investigating the TCC ability to present a panel of staphylococcal enteroxins (SE) independently of the presence of added APC. Upon exposure to a broad range of SE concentrations, MHC class II+ TCC showed an intense proliferative response even in the absence of professional APC. Diverse SE optimally stimulated responder TCC at different concentrations. The proliferation was inhibited by anti‐DR monoclonal antibodies, both in the presence and in the absence of APC. The SE activation of TCC in the absence of APC induced the same series of phenotypic variations as that observed following the TCC stimulation with APC. Irradiated TCC efficiently presented membrane‐bound SE to responder TCC as well as professional APC. These results show that a single cell of a given clone effectively presents the SE to other cells of the same clone, and provide evidence that SAg can efficiently mediate T‐T cell interaction. In addition, the possibility also exists that one cell of the clone can actually undergo an auto‐stimulation via SAg‐mediated interactions between its own TcR and MHC class II molecule. It has recently been suggested that the Vβ‐selective depletion of T cells observed in acquired immunodeficiency syndrome (AIDS) patients might be a consequence of the interaction between a human immunodeficiency virus (HIV)‐encoded SAg and T cells expressing a SAg complementary Vβ. We suggest that the hypothesized HIV‐encoded SAg might mediate T‐T cell interactions that could play a relevant role in the Vβ‐selective depletion of T lymphocytes observed in HIV‐infected patients.
Immunobiological studies on experimental visceral leishmaniasis. II. Adherent cell‐mediated down‐regulation of delayed‐type hypersensitivity response and up‐regulation of B cell activation
Authors: Basak Saroj K. , Saha Bhaskar , Bhattacharya Amal , Roy Syamal 
Published: March 2007

AbstractVisceral leishmaniasis or kala‐azar is characterized by a variety of immunopathological consequences in man. The most remarkable of these are the depression of cell‐mediated immunity and polyclonal B cell activation. The consequences observed in man could be induced in a murine model by inoculating the causative agent, Leishmania donovani. The cell‐mediated response was studied in this murine model in terms of the delayed‐type hypersensitivity (DTH) response toward leishmania antigen in a progressive infection. BALB/b (H‐2b) mice showed progressive enhancement in the DTH response, whereas BALB/c (H‐2d) mice showed strong DTH at the onset which gradually disappeared (defined as DTH‐negative phase) and reappeared again at the later stage of infection. Adoptive transfer of enriched populations of splenic T cells from infected BALB/c mice together with parasite antigen into the footpad of syngenic normal recipients produced a dramatic enhancement in the DTH response, except at the onset of the DTH‐negative phase. These observations indicate that adherent cells have a role in suppression of the cell‐mediated immune response and also that another mechanism operates at the onset of the DTH‐negative phase. This DTH‐negative phase was not caused by depletion of DTH‐mediating cells from the repertoire, but rather by suppression mediated by a subset of T cell evolved in the course of infection. Characterization on the basis of lymphokine production of the T cells mediating the DTH response and of T cells mediating suppression of the DTH response showed them to be of Th1 and Th2 type, respectively. Studies also indicated that at the onset and the later stages of infection suppression was mediated by adherent cells, but at the onset of DTH‐negative phase, in particular, suppression was mediated by Th2 cells. Furthermore, experiments also showed that adherent cells from infected mice gained another property, that of driving B cells, in a T cell‐dependent manner.
Virus infection blocks the processing and presentation of exogenous antigen with the major histocompatibility complex class II molecules
Authors: Domanico Susan Z. , Pierce Susan K. 
Published: March 2007

AbstractHelper T cell recognition of antigen requires that antigen be processed and presented by class II‐expressing antigen‐presenting cells (APC). Many antigens presented by the immune system are part of infectious organisms, for example, bacteria and viruses, which themselves may affect APC function. Here we show that infection of B cell lines as APC with viruses of two different families, namely, influenza A or vaccinia, completely block processing and presentation of an exogenous globular protein antigen pigeon cytochrome c. The block appears to be primarily within the processing pathway, as virus infection has little effect on the presentation of an antigenic peptide of pigeon cytochrome c which does not require processing. It is likely that several steps in the processing pathway are affected. Only live infectious virus, not UV‐inactivated virus blocks APC function, indicating that there is no competition of viral particles with cytochrome c for the class II processing machinery. As compared to uninfected cells, virus‐infected cells internalize less antigen bound to surface Ig but degrade a similar portion of that which enters the cell. Virus infection results in reduced protein synthesis in APC which may also be a factor in decreasing APC function. Significantly, we show that the processing of a high affinity evolutionary variant of cytochrome c from Drosophila melanogaster is reduced less by virus infection as compared to c. Such knowledge may guide the selection of antigenic epitopes in vaccine design.
Interleukin‐1 induces c‐fos and c‐jun gene expression in T helper type II cells through different signal transmission pathways
Authors: Muñoz Eduardo , Zubiaga Ana M. , Huber Brigitte T. 
Published: March 2007

AbstractInterleukin (IL)‐1 induces proliferation and expression of several protooncogenes in the T helper 2 cell line D10A. We have analyzed the signal transmission pathways activated by IL‐1 in these cells, leading to the expression of c‐jun and c‐fos. IL‐1 induced c‐jun gene transcription and mRNA expression by means of a pathway dependent on protein tyrosine kinase activity since tyrphostin, a specific inhibitor of tyrosine kinase, inhibited this induction. This mechanism of transmission signaling was independent of protein kinase C (PKC) and was linked to the 80‐kDa IL‐1 receptor (IL‐1R). In addition, phorbol esters did not induce c‐jun mRNA expression, whereas c‐fos mRNA expression mediated by IL‐1 dependent on PKC; this pathway was linked to a different, still unidentified IL‐1R that was functional in the D10A cell line.Accumulation of intracellular cAMP generated by IL‐1 through the 80‐kDa IL‐1R negatively regulated c‐fos expression which was induced by IL‐1 through PKC activation. We conclude that IL‐1 modulates the expression of c‐fos in D10A cells by occupying of two independent IL‐1R that are linked to different signal transduction pathways.