bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the porcine γδ T‐cell receptor structure and cellular distribution by monoclonal antibody PPT27
Authors: Yang H. , Parkhouse R. M. E. 
Published: March 2003

SummaryThe T‐cell receptor (TCR) is the critical structure involved in antigen recognition of T lymphocytes. Although the pig has a large proportion of circulating T lymphocytes bearing the γδ TCR, their study has been impeded due to the lack of specific antibodies. Here a monoclonal antibody (mAb) PPT27 directed to γδ TCR is described. Flow cytometry analyses showed that the mAb recognized a subset of T lymphocytes of which the majority expressed no CD2, CD4 and CD8 whilst the minority bore CD2 and CD8. The mAb precipitated a protein of 86 000 MW under non‐reducing conditions and a doublet of 43 000 MW under reducing conditions from peripheral blood T lymphocytes lysed in nonidet P‐40 buffer, whilst it precipitated the CD3–TCR complex from the cells lysed in digitonin. Further analysis revealed that the antibody recognized the majority, but not all, of the γδ T cells, suggesting that there may be more isotypes of γδ TCR than currently believed. The antibody was unable to stimulate γδ T cells to proliferate in vitro, suggesting that these cells are activated by a different activation mechanism from that of αβ T cells.
Common antigenicity between Japanese cedar (Cryptomeria japonica) pollen and Japanese cypress (Chamaecyparis obtusa) pollen, II. Determination of the cross‐reacting T‐cell epitope of Cry j 1 and Cha o 1 in mice
Authors: Ohno N. , Ide T. , Sakaguchi M. , Inouye S. , Saito S. 
Published: March 2003

SummaryWe have previously detected common antigenicity between Cry j 1 and Cha o 1 in B10.S mice. B10.S mice immunized with Cry j 1‐ or Cha o 1‐generated T cells and antibodies reactive to both allergens. In the present study, we investigated the cross‐reacting and Cry j 1‐specific T‐cell epitopes in B10.S mice. Lymph node cells from B10.S mice immunized with Cry j 1 recognized Cry j 1 p111–130, p211–230, and p310–330 as well as Cha o 1 p209–228. The existence of the cross‐reacting T‐cell epitope in Cry j 1 and Cha o 1 was confirmed by the response of newly established p211–230‐specific and Cha o 1 p209–228‐specific T‐cell lines. The minimum peptide sequence (p213–224) of the cross‐reacting T‐cell epitope was identical in Cry j 1 and Cha o 1. These findings clearly demonstrate that common antigenicity at the T‐cell level between Japanese cedar and cypress pollen allergens was caused by the existence of an identitical‐cell epitope in Cry j 1 and Cha o 1.
Dendritic cell–B‐cell interaction: dendritic cells provide B cells with CD40‐independent proliferation signals and CD40‐dependent survival signals
Authors: Wykes M. , Macpherson G. 
Published: March 2003

SummaryDendritic cells (DC) have recently been shown to play an important role in B‐cell function. We have previously shown that DC can capture and retain unprocessed antigen in vitro and in vivo, and can transfer this antigen to naive B cells to initiate antigen‐specific antibody responses. We also demonstrated that DC were providing B cells with isotype‐switch signals independent of T cells but that T‐cell help was essential for antibody production. In this study, using B cells and DC from wild type (WT) and CD40 knockout (CD40KO) mice we show that DC initiate proliferation of B cells independently of CD40, because WT or CD40KO DC could induce proliferation of WT or CD40KO B cells, but proliferation was greater in the absence of CD40. DC also provide B cells with survival signals as WT DC improved viability of B cells after a 5‐day culture but survival was reduced in the absence of CD40 expression.
Genes predisposing to autoimmunity augment constitutive major histocompatibility complex class II‐associated presentation of the self‐antigen IgG2abin vivo
Authors: Bartnes K. , Li X. , Iwamoto M. , Izui S. , Hannestad K. 
Published: March 2003

SummaryThe self‐antigen IgG2ab is poorly presented to a γ2ab 435–451‐reactive I‐Ad‐restricted T‐cell hybridoma unless available in high concentrations or targeted to Fcγ‐ or complement receptors. Environmental factors, probably the extent of microbial challenge, profoundly influence the constitutive γ2ab/I‐Ad presentation in IgCHb, H‐2d mice. Here we report also a strong genetic impact. Constitutive presentation was highly efficient in spleen and thymus of (NZB × BXSB)F1 mice, which inherit a predisposition to develop lupus. Presentation correlated with disease progression and the serum levels of IgG2ab and IgG2ab complement factor 3 complexes. The finding that constitutive presentation was by far most efficient in males indicated that it was augmented by the Y chromosome‐linked autoimmune acceleration Yaa gene. In line with previous data for healthy mice, constitutive γ2ab/I‐Ad presentation was most pronounced in the adherent spleen cell fraction and improved by further enrichment for dendritic cells. Notably, however, whereas in normal mice the γ2ab determinant was undetectable on B cells lacking surface IgG2ab, such B cells contributed considerably to constitutive presentation in (NZB × BXSB)F1 hybrids. Presumably this resulted from complement receptor‐mediated internalization of IgG2ab‐containing immune complexes formed in lupus. These data add to the evidence that B cells with self‐reactive receptors, known to exist in the mature repertoire, may present non‐cognate foreign antigen to anti‐foreign helper T lymphocytes and thus differentiate into autoantibody‐secreting cells, and might likewise account for the polyclonal B‐cell activation characteristic of several autoimmune syndromes.
Natural killer 1.1+αβ T cells in the periimplantation uterus
Authors: Dang Y. , Beckers J. , Wang C.‐R. , Heyborne K. D. 
Published: March 2003

SummaryWhen the developing embryo implants into the uterine wall, resident maternal immune cells may encounter antigens present on the fetal tissues. The nature and constituents of the ensuing maternal immune response, and its regulation, are of considerable interest in understanding normal and abnormal pregnancy. Here, we report the presence of natural killer (NK)1.1+αβ T cells in the murine periimplantation uterus. These cells account for a large portion of both the T‐cell and natural killer cell populations in early pregnancy, while their numbers in the non‐pregnant uterus and later in pregnancy are greatly reduced. Phenotypically, these NK1.1+αβ T cells belong to a previously described subset of cells that bear a Vα14‐Jα281‐encoded T‐cell receptor. Unlike other organs, where both CD4+ and CD4−/CD8− NK1.1+αβ T cells are found, the placental/decidual population appears to be entirely CD4−/CD8−. The Vβ repertoire of the placental/decidual population is also altered from that of other organs, with a majority of cells expressing Vβ3. Together, these features suggest the possibility of local development. NK1.1+αβ T cells are known to recognize the class I‐like CD1 molecule. Consistent with this association, we demonstrate CD1 expression by tissues within the pregnant uterus. Our findings define an additional organ‐specific immune environment where NK1.1+αβ T cells may play a role, and continue to demonstrate the specialized nature of the maternal intrauterine immune system during pregnancy.
Expression of kininogens in the connective tissue‐type mast cells of the rat
Authors: Hosoi K. , Matsuura S. , Tsumura K. , Wei W. , Parvin M. N. , Tada J. , Akamatsu T. , Kanamori N. , Suzuki K. 
Published: March 2003

SummaryThe connective tissue‐type mast cells present in the submandibular gland (SMG) and peritoneal cavity of rats were found to express kininogens (KGs), the expression of which was demonstrated by Western blotting, reverse transcription–polymerase chain reaction (RT–PCR), RT–PCR Southern blotting, and light‐ and electron‐microscopic immunocytochemistry. In the SMG, the analysis of cDNA amplified by RT–PCR revealed that the molecular species of mRNAs expressed were high‐molecular‐weight (HMW)‐K KG and T‐I KG. Light microscopic immunocytochemistry exclusively localized the KG protein(s) in the mast cells present in the SMG. The signals in the mast cells were very strong, but no positive reaction was observed in the granular convoluted tubular cells, acinar cells or striated duct cells. As determined by using electron microscopy, extremely strong labelling with immunogold was observed in the secretory granules of the mast cells, but no labelling in their nucleus or cytoplasm. Analysis by Western blotting and RT–PCR Southern blotting indicated that both protein and mRNA of KGs were present in the mast cells separated from the peritoneal cavity, indicating de novo synthesis of KG in these cells. Preliminary experiments implied that the connective tissue‐type mast cells in other rat tissues also expressed KG.
The gills are an important site of iNOS expression in rainbow trout Oncorhynchus mykiss after challenge with the Gram‐positive pathogen Renibacterium salmoninarum
Authors: Campos‐perez J. J. , Ward M. , Grabowski P. S. , Ellis A. E. , Secombes C. J. 
Published: March 2003

SummaryFollowing injection challenge of rainbow trout with the Gram‐positive pathogen Renibacterium salmoninarum, serum nitrate levels increased indicative of NO production. The timing and amount of nitrate produced varied with the virulence of the bacterial strain used, with the highest levels seen in fish challenged with the most virulent (autoaggregating) strain. Immunization with a killed R. salmoninarum preparation in Freund’s incomplete adjuvant significantly increased nitrate levels after challenge. Inducible nitric oxide synthase (iNOS) transcript expression was detectable in rainbow trout tissues after injection challenge with R. salmoninarum, and its induction in the gills was both quick (between 3 and 6 hr) and relatively prolonged (lasting several days). iNOS expression in the kidney was also seen at a later stage (24 hr) but appeared to switch off relatively rapidly. Bath challenge with R. salmoninarum also induced iNOS expression in gill, and a variable expression in the gut and kidney also occurred. These results highlight the importance of the gills, not only as a point of entry of pathogens but also as a tissue capable of mounting an immune response.
Minor role played by type I tumour necrosis factor receptor in the control of Mycobacterium avium proliferation in infected mice
Authors: Silva R. A. , Gomes M. S. , Appelberg R. 
Published: March 2003

SummaryControl of mycobacterial growth depends on the concerted activity of different cytokines acting in different stages of the development of innate and adaptive immune responses. Tumour necrosis factor‐α (TNF‐α) has been shown to play a protective role in Mycobacterium avium infections. Here we assessed the growth of this mycobacterial species in wild‐type mice and in mice with a genetically engineered disruption of the type I receptor for TNF‐α (p55‐KO mice). p55‐KO mice infected with a low‐virulence strain of M. avium exhibited a slightly delayed capacity to eliminate the micro‐organisms from the liver as compared with wild‐type animals. However, either the growth of this strain in the other organs studied (spleen and lung) or the growth of two other strains of M. avium with intermediate or high virulence, failed to be affected by mutation of the TNF‐α receptor. p55‐KO mice were also as protected by the administration of recombinant interleukin‐12 as the heterozygous p55 +/– mice. We conclude that signalling through the type I TNF receptor plays a small role in vivo in the induction of mycobacteriostasis during M. avium infection but may improve survival during infection with virulent mycobacteria, independently of the extent of their proliferation.
Soluble L‐selectin levels in type I diabetes mellitus: a surrogate marker fordisease activity?
Authors: Krętowski A. , Gillespie K. M. , Bingley P. J. , Kinalska & I. 
Published: March 2003

SummaryL‐selectin (CD62L) is a cell adhesion molecule which plays a key role in the initiation of leucocyte migration from blood vessels to sites of local inflammation. The aim of this study was to investigate T‐lymphocyte expression of CD62L antigen and serum levels of soluble L‐selectin (sL‐selectin) in subjects with clinical and preclinical type I diabetes to determine whether they could provide surrogate markers for disease activity. CD62L selectin expression on memory T lymphocytes was studied by cytometric analysis in 22 patients with newly diagnosed type I diabetes, 20 first‐degree relatives of patients with type I diabetes, 14 patients with Graves’ disease, and 22 healthy controls. sL‐selectin levels were measured by enzyme‐linked immunosorbent assay (ELISA) in enlarged groups of subjects in these categories, as well as in patients with long‐standing type I diabetes, treated Graves’ disease and type II (non‐insulin dependent) diabetes. L‐selectin levels were also related to islet autoantibodies, human leucocyte antigen (HLA) genotype and L‐selectin T668C gene polymorphisms. L‐selectin expression on memory T lymphocytes was reduced in newly diagnosed diabetes and islet autoantibody positive siblings compared with controls. sL‐selectin levels were significantly raised in newly diagnosed type I diabetes compared with controls, with intermediate levels in family members, both with and without islet autoantibodies, and in long‐standing type I diabetes. Levels were also raised in patients with untreated Graves’ disease. Patients with type II diabetes had sL‐selectin levels which did not differ from controls. sL‐selectin levels correlated with the presence of diabetes‐associated HLA alleles in both family members and controls; levels also fell with increasing age in family members. Multiple regression analysis showed that HLA genotype and age were independent determinants of sL‐selectin levels. sL‐selectin levels are raised at the time of diagnosis of type I diabetes and Graves’ disease and appear to be modulated by disease activity, but levels are determined predominantly by HLA‐associated genetic susceptibility and age. sL‐selectin may provide a late marker of autoimmune destruction of islets and sequential measurement may be useful in monitoring disease activity and the effect of interventions preceding type I diabetes.
Differential effects of CD4 and CD8 engagement on the development of cytokine profiles of murine CD4+ and CD8+ T lymphocytes
Authors: Campbell S. B. , Komata T. , Kelso A. 
Published: March 2003

SummaryA simple culture system devoid of antigen‐presenting cells was used to examine the ability of immobilized antibodies to lymphocyte function‐associated antigen‐1 (LFA‐1) (CD11a), CD28 and CD4 or CD8 to modulate the responses of normal murine CD4+ and CD8+ lymph node T cells to immobilized anti‐CD3 antibody and interleukin‐2 (IL‐2). All the antibodies enhanced proliferative responses to limiting anti‐CD3 antibody. Both CD4+ and CD8+ cells produced substantial titres of IL‐3 and interferon‐γ (IFN‐γ) in primary and secondary cultures regardless of the coactivating antibodies used for priming. By contrast, the combination of anti‐CD4 with anti‐CD3 antibody stimulated significantly higher titres of IL‐4 than any other antibody combination in cultures of CD4+ cells. This CD4‐dependent IL‐4 response was induced in CD4+ T cells of naive (CD44low) phenotype and was similar in magnitude to the response induced by exogenous IL‐4 but, unlike the latter, was not associated with elevated IL‐3 synthesis. A comparable effect of anti‐CD8 antibodies on CD8+ cells was not observed: although IL‐4 production by CD8+ cells was induced by exogenous IL‐4, it was not detected following coactivation with anti‐CD8 or any other antibodies. We conclude that anti‐CD4 antibody is a potent inducer of IL‐4‐secreting CD4+ T cells whose effects can be distinguished from those of anti‐CD8 antibody on CD8+ T cells and from those of IL‐4 on either subset.
Functional activity of CD40 antibodies correlates to the position of binding relative to CD154
Authors: Barr T. A. , Heath A. W. 
Published: March 2003

SummaryIn this study we describe the characterization of a panel of 12 anti‐mouse CD40 monoclonal antibodies (mAb). Characterization was performed in terms of antibody‐binding site relative to the CD154 ligand, and the relationship between position and functional outcome of binding. The antibodies divided into three groups. The first were strong inhibitors of CD154 binding, and induced strong proliferative and activation signals to B cells. Two antibodies gave intermediary inhibition and comparable levels of activation. The remaining antibodies were found to bind outside the CD154 binding site and were poor inducers of B‐cell activation. Data presented show a strong correlation between location of mAb binding and the resultant activation signal delivered. This correlation is shown to be independent of the isotype of the antibody involved and of its affinity. Implications of these findings are discussed.
Persistent infection with Listeria monocytogenes in the kidney induces anti‐inflammatory invariant fetal‐type γδ T cells
Authors: Ikebe H. , Yamada H. , Nomoto M. , Takimoto H. , Nakamura T. , Sonoda K.‐H. , Nomoto K. 
Published: March 2003

SummaryAfter intraperitoneal inoculation with Listeria monocytogenes, γδ T cells appear in the peritoneal cavity preceding the appearance of αβ T cells. Such γδ T cells predominantly express T‐cell receptor (TCR)Vγ1/Vδ6, develop through an extrathymic pathway, and contribute to host defence against the bacteria. We have observed a gradual increase in γδ T cells in kidneys of mice after intrarenal inoculation with L. monocytogenes, which resulted in an unusually long‐lasting local infection. In this study, we examined the characteristics and the roles of the γδ T cells induced in this model. It was found that these γδ T cells predominantly expressed TCRVγ6/Vδ1 with canonical junctional sequences identical to those expressed on fetal thymocytes. Although depletion of such γδ T cells in vivo did not affect the number of bacteria, it resulted in histologically exacerbated inflammation in the kidneys. These results indicate that a persistent infection with L. monocytogenes in kidneys induces a different kind of γδ T cell from that induced after intraperitoneal infection. The former expresses invariant fetal‐type Vγ6/Vδ1+TCR and plays a regulatory role in resolution of inflammation.
Induction of in vivo resistance to Mycobacterium avium infection by intramuscular injection with DNA encoding interleukin‐18
Authors: Kim S. H. , Cho D. , Kim T. S. 
Published: March 2003

SummaryInterferon‐gamma (IFN‐γ) is closely associated with the generation of cell‐mediated immunity and resistance to intracellular parasites. Interleukin‐18 (IL‐18) was known to strongly induce IFN‐γ production by T cells and natural killer (NK) cells. In order to determine whether injection with DNA encoding IL‐18 can stimulate the resistance to Mycobacterium avium complex (MAC) infection, the mature IL‐18 cDNA with κ leader sequence was cloned under control of the cytomegalovirus (CMV) promoter (TcCMVIL‐18) and its effect on MAC infection was investigated in genetically susceptible BALB/c mice. Injection with the TcCMVIL‐18 DNA during intranasal infection with MAC resulted in a significant decrease in bacterial load of lung during the entire 8‐week observation period, while injection with the TcCMV control DNA did not. Lung cells in mice injected with the TcCMVIL‐18 DNA showed persistent production of IFN‐γ throughout the 8‐week period. Furthermore, immunization with the TcCMVIL‐18 DNA induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by lung cells than immunization with the TcCMV control vector. This work suggests that IL‐18 DNA vaccination may be useful in the immunotherapeutic or immunoprotection approaches of infections by intracellular parasites such as mycobacteria.
Systematic characterization of human CD8+ T cells with natural killer cell markers in comparison with natural killer cells and normal CD8+ T cells
Authors: Ohkawa Takashi , Seki Shuhji , Dobashi Hiroshi , Koike Yuji , Habu Yoshiko , Ami Katsunori , Hiraide Hoshio , Sekine Isao 
Published: March 2003

SummaryWe investigated the function of CD56+ CD8+ T cells (CD56+ T cells) and CD56− CD57+ CD8+ T cells (CD57+ T cells; natural killer (NK)‐type T cells) and compared them with those of normal CD56− CD57− CD8+ T cells (CD8+ T cells) and CD56+ NK cells from healthy volunteers. After the stimulation with immobilized anti‐CD3 antibodies, both NK‐type T cells produced much larger amounts of interferon‐γ (IFN‐γ) than CD8+ T cells. Both NK‐type T cells also acquired a more potent cytotoxicity against NK‐sensitive K562 cells than CD8+ T cells while only CD56+ T cells showed a potent cytotoxicity against NK‐resistant Raji cells. After the stimulation with a combination of interleukin (IL)‐2, IL‐12 and IL‐15, the IFN‐γ amounts produced were NK cells ≥ CD56+ T cells ≥ CD57+ T cells > CD8+ T cells. The cytotoxicities against K562 cells were NK cells > CD56+ T cells ≥ CD57+ T cells > CD8+ T cells while cytotoxicities against Raji cells were CD56+ T cells > CD57+ T cells ≥ CD8+ T cells ≥ NK cells. However, the CD3‐stimulated proliferation of both NK‐type T cells was smaller than that of CD8+ T cells partly because NK‐type T cells were susceptible to apoptosis. In addition to NK cells, NK‐type T cells but not CD8+ T cells stimulated with cytokines, expressed cytoplasmic perforin and granzyme B. Furthermore, CD3‐stimulated IFN‐γ production from peripheral blood mononuclear cells (PBMC) correlated with the proportions of CD57+ T cells in PBMC from donors. Our findings suggest that NK‐type T cells play an important role in the T helper 1 responses and the immunological changes associated with ageing.
Influence of CD4 or CD8 deficiency on collagen‐induced arthritis
Authors: Ehinger Magnus , Vestberg Mikael , Johansson Åsa C. M. , Johannesson Martina , Svensson Anders , Holmdahl Rikard 
Published: March 2003

SummaryThe role of T cells in the mouse collagen‐induced arthritis (CIA) model for rheumatoid arthritis is not clarified, and different results have been reported concerning the role of CD4 and CD8 T cells. To address this issue, we have investigated B10.Q mice deficient for CD4 or CD8. The mice lacking CD4 were found to be less susceptible to disease, but not completely resistant, whereas the CD8 deficiency had no significant impact on the disease. No difference in the development of late occurring relapses was noted. Interestingly, the CD4‐deficient mice had a severely reduced response to the glycosylated form of the immunodominant type II collagen (CII) 256–270 peptide whereas the response to the non‐glycosylated peptide was not significantly different. Furthermore, CD4‐deficient mice had lower antibody responses to CII, explaining the lower disease susceptibility. In comparison with previously reported results, it is apparent that the lack of CD4 molecules has a different impact on CIA if present on different genetic backgrounds, findings that could possibly be related to the occurrence of different disease pathways of CIA in different mouse strains.