摘要:

AbstractLocal cytokine gene expressionin vivowas analyzed by direct analysis of RNA obtained from salivary gland tissues of MRL/lpr mice with autoimmune sialadenitis. The expression of cytokine genes were assessed by the reverse‐transcriptase polymerase chain reaction, and by immunohistochemical analysis. The expression of interleukin‐1(IL‐1)β and tumor necrosis factor was detected before the onset of inflammatory lesions in the salivary glands of mice of 1 or 2 months of age, and IL‐6 mRNA expression was clearly detected at the time of onset of typical autoimmune sialadenitis at 3 months of age in MRL/lpr mice, and was up‐regulated with advancing age. These results suggest that the overexpression of these inflammatory cytokine genes is involved in the development and progression of organ‐localized autoimmunity in the salivary glands of

ISSN:0014-2980    

DOI:10.1002/eji.1830231002

出版商:WILEY‐VCH Verlag GmbH    

年代:1993

数据来源: WILEY

摘要:

AbstractLeukotriene B4(LTB4) has been shown to affect several interleukin (IL)‐linked functions of human lymphocytes. In this study, we investigated whether LTB4regulates IL‐5 generation from human T cells and subsequently modulates eosinophil functions. Preincubation of T cells with very low concentrations (10−12to 10−8M) of LTB4induced concentration‐dependent IL‐5 production, the event occurring after the first 24 h of cultivation. However, direct action of LTB4to IL‐5 generation is strictly dependent on a preincubation with appropriate concentration of LTB4. In contrast, the stereoisomer of LTB4,5S,12S‐dihydroxy‐6,8,10,14‐eicosatetraenoic acid showed no enhancement of IL‐5 production. IL‐5 released from LTB4‐primed T cells elicited sustained viability of mature eosinophils and reduced the content of eosinophil cationic protein in their crystalloid matrix by degranulation. These data suggest that LTB4induces bioactive IL‐5 production from T cells and that the released IL‐5 modulates eosinophil functions which might play a crucial role in eosinophil‐linke

ISSN:0014-2980    

DOI:10.1002/eji.1830231003

出版商:WILEY‐VCH Verlag GmbH    

年代:1993

数据来源: WILEY

摘要:

AbstractTo determine the role of encephalitogenic T cells in the formation of lesions in the central nervous system (CNS), experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats by immunization with either myelin basic protein (MBP) or the synthetic peptide which corresponds to the 87–100 sequence of guinea pig MBP, and T cells expressing T cell receptor (TcR) Vβ8.2, Vβ8.5, Vβ10 and Vβ16 in the lymphoid organs and CNS were localized and quantified by flow cytometry (FCM) and immunohistochemistry. In normal rats, the percentage of T cells expressing these Vβ phenotypes to the total number of TcR αβ+T cells, as determined by FCM, ranged from 5% to 10% in the lymph node. Vβi6+T cells were the most predominant population among the four Vβ subsets tested. Essentially the same findings were obtained from the analysis of the lymphoid organs of rats with EAE which had been induced by immunization with the same two antigens. In sharp contrast, 15–20% of the T cells isolated from lesions of MBP‐induced EAE expressed Vβ8.2+. Thus, the percentage of Vβ8.2+T cells in the EAE lesions was threefold higher than that in the lymph node, while the proportions of Vβ8.5+, Vβ10+and Vβ16+T cells were about the same in both organs. The predominance of Vβ58.2+T cells in EAE lesions was confirmed by counts of immunohistochemically stained T cells in the spinal cord. Moreover, it was revealed that (i) the predominance of Vβ8.2+T cells was greatest during the development of EAE and became less obvious at the recovery stage, and (ii) at the peak stage of EAE, approximately 85% of Vβ8.2+T cells were distributed in the parenchyma while 15% were in the perivascular space of the CNS vessels. These findings indicate that encephalitogenic T cells which express Vβ8.2 infiltrate the CNS at a very early stage of EAE and become the predominant population in infiltrating T cells, and further suggest that encephalitogenic T cells, not only recruit inflammatory cells in the CNS, but also cause neural tissue damage

ISSN:0014-2980    

DOI:10.1002/eji.1830231004

出版商:WILEY‐VCH Verlag GmbH    

年代:1993

数据来源: WILEY

摘要:

AbstractThe CD38 antigen displays restricted functional associations with surface molecules involved in immune system and complement. Capping of the CD38 molecule in normal or neoplastic T cells is followed by rapid and specific co‐modulation of the CD3‐Tcell receptor (TcR) complex. In normal and tumor cells of B lineage, CD38 was found to be also associated with surface Ig (sIg) and with the complement receptor 2 (CR2)/CD19 complex. The CD38 molecule expressed by purified natural killer cells displayed an association with the low affinity IgG Fc receptor (FcγRIII) CD16. These observations suggest that specialized areas in the plasma membrane contain co‐modulating structures, including different receptors involved in the transduction of extracellular signals. We propose a model whereby TcR, CR2 and CD16 are ligand binding structures in their respective lineages, while CD38 is a molecule involved in the intracellular transduction of the s

ISSN:0014-2980    

DOI:10.1002/eji.1830231005

出版商:WILEY‐VCH Verlag GmbH    

年代:1993

数据来源: WILEY

摘要:

AbstractSignificant immigration of peripheral T cells into SCID thymus was observed following reconstitution with normal Peyer's patch, mesenteric lymph node or peripheral lymph node cells. Immunohistologic and flow cytometric analyses reveal that T cells from these tissues are found in the thymus for as long as 177 days and can account for up to 67% of intrathymic cells. The returning cells express the CD3/Tcell receptor α/β complex, indicative of mature cells, and are equally divided among helper (CD4+CD8 ) and cytotoxic (CD4−/CD8+) phenotypes. The immigration of peripheral T cells is not accompanied by the appearance of immature, double‐positive (CD4+CD8+) thymocytes as seen in similar reconstitutions using bone marrow. Taken together, these results suggest that peripheral T cells from a variety of lymphoid organs may regularly re‐enter the thymus and, thus, possibly play a role in normal thymic deve

ISSN:0014-2980    

DOI:10.1002/eji.1830231006

出版商:WILEY‐VCH Verlag GmbH    

年代:1993

数据来源: WILEY

摘要:

AbstractRecently, we have described that anti‐IgM antibodies profoundly inhibited the growth of BKS‐2, an immature B cell lymphoma. In this report, we demonstrated that ionomycin alone at very low concentrations (20 nM) inhibited the growth of BKS‐2 cells completely. The levels of intracellular Ca2+induced by the inhibitory concentrations of ionomycin were comparable to those in anti‐IgM‐treated cells. The growth inhibition caused by ionomycin was reversed by phorbol 12‐myristate 13‐acetate and lipopolysaccharide. In addition, the immunosuppressants, cyclosporin A and FK506 conferred significant protection from the negative signal induced by ionomycin. However, either cyclosporin A, FK506 or lipopolysaccharide was not found to have direct effect on ionomycin‐induced Ca2+mobilization in BKS‐2 cells. Also, ionomycin augmented the anti‐IgM‐induced growth arrest in these cells. Furthermore, BKS‐2 cells that were exposed to anti‐IgM or ionomycin underwent apoptosis as characterized by DNA fragmentation. Thus, the characteristics of growth inhibition induced by ionomycin and anti‐IgM appeared to be similar in that phorbol 12‐myristate 13‐acetate, lipopolysaccharide, cyclosporin A and FK506 caused significant reversal from such negative signals and both ionomycin and anti‐IgM induced apoptosis in these cells. Altogether, these results showed that the elevation of intracellular Ca2+alone was sufficient to inhibit th

ISSN:0014-2980    

DOI:10.1002/eji.1830231007

出版商:WILEY‐VCH Verlag GmbH    

年代:1993

数据来源: WILEY

摘要:

AbstractWe have previously described a monoclonal antibody (mAb), CZ‐1, which reacts with an epitope expressed on most peripheral basophils, natural killer cells, B cells, and CD8+T cells, but not with most thymocytes or peripheral CD4+T cells. Here we show that mAb CZ‐1 defines a sialic acid‐dependent epitope associated with a subpopulation of CD45 molecules. This conclusion is based on the ability to block binding of mAb CZ‐1 by sialic acid, neuramin‐lactose, neuraminidase, and mAb to CD45RB, and by expression of the epitope on transfected W2 cells expressing exon B of CD45. The results suggest that the CZ‐1 epitope is a post‐translational modification expressed on a subpopulation of the CD45 molecules also expressing the B exon. Expression of the CZ‐1 epitope was required for freshly isolated lymphocytes to respond to interleukin‐2 (IL‐2). Depletion of CZ‐1+cells by C or by cell sorting of thymocytes or splenocytes eliminated the IL‐2 responsive cells. The subpopulations of thymocytes and CD4+splenocytes responding to IL‐2 were exclusively within the small CZ‐1+subpopulation. mAb CZ‐1 was also used to subdivide CD45+and CD45RB+splenocytes into IL‐2‐responsive and ‐nonresponsive subpopulations. The CZ‐1 epitope was also expressed on virtually all lymphokine‐activated killer cell precursors. These data, thus, indicate that cells responsive to IL‐2 e

ISSN:0014-2980    

DOI:10.1002/eji.1830231008

出版商:WILEY‐VCH Verlag GmbH    

年代:1993

数据来源: WILEY

摘要:

AbstractDDD/1 (DDD) mice were characterized by marked paucity of T cells in lymph nodes (LN). InDDD‐Mtv‐2/Mtv‐2(DDD‐Mtv‐2) congenics, T cells were 4‐ to 18‐fold increased depending on ages but B cells doubled at the most. Thymus weight also increased. In DDDfDDD‐Mtv‐2, DDD neonatally infected withMtv‐2‐derived exogenous MMTV (MMTV‐2), neither LN cells nor thymus weight increased. The Vβ5+and Vβ8+Tcell contents in LN were practically the same among three strains. TheMtv‐2‐induced expansion of LN Tcells was polyclonal and appeared indigenous to DDD mice. BothMtv‐2and MMTV‐2 induced progressive age‐dependent deletion of Vβ14+CD4+LN cells.Mtv‐2but not MMTV‐2 caused deletion of Vβ14+CD8+ LN cells and mature Vβ14+CD4+thymocytes. Thus,Mtv‐2‐and MMTV‐2‐induced Vβ14+T cell deletion may reflect intrathymic and peripheral elimination, respectively. The absence of I‐E gene expression in DDD indicates that Vβ14+T cell deletion advances inde

ISSN:0014-2980    

DOI:10.1002/eji.1830231009

出版商:WILEY‐VCH Verlag GmbH    

年代:1993

数据来源: WILEY

摘要:

AbstractThe mechanism of antigen‐specific suppression and reasons for aberrant major histocompatibility complex (MHC) class II restriction mediated by CD8+T cells was investigated in a previously reported murine model of immunosuppression, generated by intraperitoneal priming withMycobacterium vaccae. Both the CD4+T helper cells (Th) and CD8+T supressor cell (Ts) ofM.vaccae‐primed mice recognized the 65‐kDa antigen of the bacillus, presented by I‐A and I‐E, respectively. The CD8+Tscould inhibit non‐antigen‐specific proliferation of primed CD4+T cells induced by the exogenously added interleukin (IL)‐2 (concanvalin A‐stimulated culture supernatant). For inhibition, the Tshad to be activated by the 65‐kDa antigen. The degree of inhibition was dependent upon the amount of added IL‐2 and the relative numbers of primed CD8+and CD4+T cells. On incubation with antigen‐presenting cells, and the 65‐kDa antigen, the primed CD8+T cells absorbed IL‐2 as efficiently as primed CD4+T cells. Based on this, it was concluded that the primed CD8+T cells induced suppression by competition for IL‐2.Employing the same model, the MHC restriction of recognition of the suppressor epitope of the 65‐kDa antigen by the CD8+Tswas investigated. The epitopes presented by diverse MHC class II molecules, such as self I‐A, I‐E and even allogeneic I‐E were similar, because they were recognized by the same population of primed CD8+Ts. Further, immunization of C57BL/6 mice with Ltk‐cells expressing H‐2 DkKkalloantigens, stimulated CD8+T cells capable of recognizingM.vaccae65‐kDa antigen. Based on these data, it was proposed that recognition of the suppressor epitope of the 65‐kDa antigen by the primed CD8+Tsexhibits lack of res

ISSN:0014-2980    

DOI:10.1002/eji.1830231010

出版商:WILEY‐VCH Verlag GmbH    

年代:1993

数据来源: WILEY

摘要:

AbstractWe have isolated a number of new allelic variants of the unique functional genes encoding chicken immunoglobulin heavy and light chain variable regions (VH1andVL1, respectively). The distribution and nature of nucleotide variation among these and previously identifiedVH1andVL1alleles demonstrates that random point mutations are likely not the predominant cause of allelic variation at these loci. Comparison of the variant nucleotides with sequences from the pseudo‐VHand pseudo‐VLgene families, which lie 5′ toVH1andVL1, respectively, suggests that the great majority of allelic variants can be accounted for by segmental transfer of sequence from donor pseudogenes into the germ‐lineVH1andVL1genes. These results demonstrate that the chickenVH1andVL1genes are susceptible to sequence replacement at the germ‐line level as well as somatically during antibody diversification. The limited repertoire of Bcell specificities produced by gene rearrangement in the chicken has led to speculation that these specificities may play a critical role in the progression of chicken B cell development. The results presented here do not support this hypothesis since many of the allelic variant nucleotides described here encode non‐conservative amino acid substitutions within the antigen‐binding sites of th

ISSN:0014-2980    

DOI:10.1002/eji.1830231011

出版商:WILEY‐VCH Verlag GmbH    

年代:1993

数据来源: WILEY