摘要:

AbstractHuman natural killer (NK) cells can be subdivided into two populations based on the density of cell surface CD56 antigen. The great majority (∼ 90%) of NK cells express CD56 at low levels (the CD56dimphenotype), whereas a small NK cell subset (∼ 10%) exhibits approximately fivefold greater density of surface CD56. Exposure to exogenous interleukin 2 (IL 2) induces tenfold greater proliferation of CD56brightcells compared to CD56dimlymphocytes, even though both subsets constitutively express similar levels of intermediate affinity IL 2 receptor (IL 2R) p75 chains. Incubation with IL 2 alone or irradiated target cells alone could induce expression of the IL 2R p55 chain by both CD56brightand CD56dimNK cells; a combination of both stimuli was most effective. IL 2R p55 induction was evident after co‐culture of NK cells with both NK‐sensitive and NK‐resistant cell lines or with antibody‐coated target cells. Activation of NK cells with IL 2 plus target cells resulted in enhanced proliferation compared to activation with IL 2 alone; target cells alone did not induce significant proliferation. Although both NK cell subsets appeared to express high‐affinity IL 2R p75/p55 heterodimers after stimulation with target cells and IL 2, proliferation of CD56dimcells remained minimal after such activation; activated CD56dimcells consistently demonstrated less proliferation to IL 2 than did resting CD56brightcells. In contrast, CD56brightNK cells exhibited even greater proliferation after stimulation with target cells. Almost all CD56dimNK cells expressed CD16 (FcγR III) as well as the NK ζ chain, whereas<50% of CD56brightcells express either CD16 or ζ. CD56brightand CD56dimlymphocytes, thus, appear to represent distinct subpopulations of NK cells with different functional activities. Unlike CD56brightcells, CD56dimNK cells do not proliferate optimally to IL 2, even after the latter have been stimulated to express both IL 2R p55 and IL 2R p75. Efficient proliferation of CD56dimNK cells may, thus, require additional or alt

ISSN:0014-2980    

DOI:10.1002/eji.1830220102

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractThe adhesion of T cells to components of the extracellular matrix (ECM) is mediated by the β1subfamily of integrin receptors, designated VLA. It has been recently demonstrated that the binding of VLA receptors to protein components of the ECM is rapidly augmented by the activation of the T cells without, however, any actual change in the level of expression of the VLA receptors for fibronectin (FN) or laminin (LN). Thus, it is likely that activation of existing VLA receptors is required for binding. The activation must be regulated by T cell surface molecules capable of transducing signals into the cell. We studied the role of the CD4 molecule in the binding of rat CD4+T cells to the FN and LN components of the ECM. We now report that the CD4 molecule appears to play a major role in regulating T cell interactions with ECM. This conclusion is based on the following observations: (a) monoclonal antibodies directed against the CD4 molecule inhibited T cell adhesion to both FN and LN; (b) down‐regulation of the CD4 molecule resulted in partial loss of the ability of CD4+T cells to adhere to FN and LN; (c) a CD4+T cell clone adhered to both FN and LN while a CD4−CD8−clone expressing an identical T cell receptor bound weakly to both proteins and (d) treatment of the CD4+T cells with an inhibitor of the CD4‐associated tyrosine protein kinase activity inhibited T cell adhesion to both ECM

ISSN:0014-2980    

DOI:10.1002/eji.1830220103

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractLy‐6A.2 (T cell‐activating protein, TAP) and Thy‐1 are glycosyl‐phosphatidylinositol (GPI)‐anchored proteins expressed on the surface of murine T lymphocytes. We have found that Ly‐6A.2 (TAP) and Thy‐1 are internalized by T cells. In the present study we have investigated whether these GPI‐anchored proteins enter cells by endocytosis through coated pits. Two lines of evidence argue against the involvement of coated pits in the internalization of Ly‐6A.2 (TAP) and Thy‐1. First, drugs that effectively blocked the endocytosis of transferrin receptor and H‐2 class I molecules, (which are known to be internalized via coated pits) did not inhibit the internalization of the GPI‐anchored proteins. Second, in ultrastructural analyses, Ly‐6A2 (TAP) and Thy‐1, in contrast to the transferrin receptor, were rarely found in coated pits or vesicles. These observations suggest that the GPI‐anchored proteins on T lymphocytes are internalized by a distinct pathway that does not involve en

ISSN:0014-2980    

DOI:10.1002/eji.1830220104

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractIn this study, specific antibodies against natural killer (NK) cell surface markers identify these cells to be commonly present in normal intestinal mucosa of inflammatory bowel disease (IBD) and carcinoma patients. Cells expressing the CD56 adhesion molecule were found to be far more abundant than CD16+cells. Functional studies revealed that cells mediating non‐major histocompatibility complex‐restricted cytotoxicity (NK activity) in the lamina propria express the CD56 surface antigen, whereas only a minority of this activity resides in the population with CD16 expression. This is in contrast with peripheral blood NK cells, which were found to be almost exclusively both CD16+and CD56+. Moreover, in the lamina propria of the intestine we found CD3+T lymphocytes not to be involved in spontaneous cell‐mediated killing of tumor cells.Considerably higher numbers of cells with the CD16 or CD56 surface markers were found to be present in normal mucosa of IBD patients compared with normal mucosa of carcinoma patients, which was also reflected in higher levels of cytotoxicity detected in lamina propria mononuclear cell preparations from normal IBD mucosa. Because of the disease‐related localization of the mucosa studied from both patient groups,i.e.ileumvs.colon, the observed differences may be related to tissue characteristics. Within the IBD group, relatively high levels of cytotoxicity were found in cell preparations from normal mucosa of Crohn's disease patients compared with ulcerative colitis patients, which might support the current concept that Crohn's disease affects the whole of the gastrointestina

ISSN:0014-2980    

DOI:10.1002/eji.1830220105

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractThe VpreBgenes, which encode surrogate immunoglobulin light chain molecules, are expressed as RNA almost exclusively in pre‐B cells. We have investigated the transcriptional control mechanisms which are responsible for the pre‐B cell‐specific RNA expression of the mouse VpreB1and VpreB2genes. Nuclear run‐on analyses demonstrate that the pre‐B cell‐specific expression of both VpreBgenes is controlled primarily at the level of initiation of transcription. S1 nuclease protection‐mapping defined two or three major start sites of transcription for the VpreBgenes. To find a promoter and other potential cis‐acting regulatory elements, a 700‐bp fragment 5′ of the transcription start sites of the VpreB1gene was used in gene transfer experiments and found to act as a promoter in pre‐B lymphocytes. Deletion experiments showed that 191 bp upstream of the most 5′ transcription start site is required for the pre‐B cell promoter activity. DNA sequence analysis of the 5′ region of the mouse VpreB1, VpreB2and human VpreBgenes reveal that this region of approximately 200 bp is strongly conserved. This 200‐bp promoter region contains several conserved nucleotide sequence motifs which may act to mediate the pre‐B cell‐specifi

ISSN:0014-2980    

DOI:10.1002/eji.1830220106

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractThe VpreB1protein is thought to be expressed on the surface of pre‐B cells in association with λ5and μ, heavy chain, and to play an important role on B cell differentiation. The expression of VpreB1and λ5is pre‐B cell specific, and regulated at the initiation of transcription. We have identified at least two sequence‐specific DNA‐binding proteins which bind to the region −191 to ‐74 of the promoter of the mouse VpreB1gene. These DNA‐binding proteins also bind to the promoter of the mouse λ5gene. One of the two DNA‐binding proteins, called EBB‐1, is restricted to pre‐B and B cells, but not detected in plasma cells, T cells and cells of other lineages. Transient transfection analysis of reporter constructs revealed that the binding sites of these proteins play a significant role in the activity of the promoter, especially the binding site of EBB‐1. Taken together these results suggest that EBB‐1 might be one of the crucial factors which regulates a series of intracellular event

ISSN:0014-2980    

DOI:10.1002/eji.1830220107

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractAn immediate consequence of T cell activation via the T cell receptor (TcR)/CD3 complex and CD2 antigen is the hydrolysis of phosphatidylinositol‐(4,5)‐bisphosphate and the generation of inositol‐(1,4,5)‐trisphosphate and diacylglycerol which then regulate intracellular calcium and protein kinase C. Changes in cellular levels of phosphoinositides phosphorylated on the D‐4 and D‐5 position during T cell activation have been well documented. Recently it has been proposed that phosphoinositides phosphorylated on the D‐3 position of the inositol ring by a novel phosphoinositide (PI) 3 kinase may also be important in cell activation. In the present study we have examined the levels and regulation of D‐3 phosphoinositides in T cells activated by the TcR/CD3 complex and CD2 antigens. The data show the existence of phosphatidylinositol‐(3)‐monophosphate [PtdIns(3)P], phosphatidylinositol‐(3,4)‐bisphosphate [PtdIns(3,4)P2] and phosphatidylinositol‐(3,4,5)‐trisphosphate [PtdIns(3,4,5)P3] in T cells. Activation of the TcR/CD3 complex or CD2 antigen results in modulation of PtdIns(3,4)P2and a putative PtdIns(3,4,5)P3in T cells but does not change levels of PtdIns(3)P. These data provide the first evidence that lipid products of a P

ISSN:0014-2980    

DOI:10.1002/eji.1830220108

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractCollagen type II (CII) is a cartilage‐specific matrix compound well known as an inducer of an experimental. T cell‐dependent autoimmune arthritis, a disease which shows some similarities to human rheumatoid arthritis. Here we report on an HLA‐DR7‐restricted human CD4 T cell clone (TC9), which was isolated from a healthy donor and recognizes human CII. After screening CNBr fragments of CII and tryptic fragments derived thereof, the T cell epitope could be mapped to amino acid residues 271‐285 of the triple helical region of CII that are located within CNBr fragment 11 [α1 (II) CB11]. This epitope was confirmed by a synthetic peptide stimulatory for TC9. The T cell receptor β chain of TC9 was cloned using the polymerase chain reaction; it comprises Vβ6.7 and contains besides Jβ2.3 and Cβ2 an as yet undescribed sequence for

ISSN:0014-2980    

DOI:10.1002/eji.1830220109

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractTo investigate the role of CD4+cells in the induction and maintenance of streptococcal cell wall (SCW)‐induced arthritis, Lewis rats were treated with a monoclonal antibody against rat CD4 (W3/25). Injection before onset of the arthritis resulted in resistance to SCW arthritis. Treatment with anti‐CD4 during ongoing arthritis induced an amelioration of the arthritis, demonstrating that CD4+cells are involved in both the induction and effector phases of the chronic arthritis.After return of CD4+cells to normal levels in the circulation, no arthritis occurred in protected rats, despite the continued presence of SCW in the body. Even reinjection of SCW could not induce arthritis in these rats, suggesting that tolerance to SCW had occurred. In addition, these tolerized rats were refractory to actively induced adjuvant arthritis (AA), but were susceptible to passively transferred AA.Our data imply, that (a) treatment with anti‐CD4 plus SCW induces a long‐term resistance to SCW‐induced arthritis and adjuvant arthritis, (b) SCW andM. tuberculosismay use similar mechanisms of regulation of arthritis and (c) active peripheral suppression is not the mechanism of this nonrespo

ISSN:0014-2980    

DOI:10.1002/eji.1830220110

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractT lymphocytes derived from peripheral blood of a patient with adenosine deaminase (ADA) deficiency were expandedin vitro. The human ADA (hADA) gene was introduced into these replicating ADA−T cells with the use of an amphotropic recombinant retrovirus carrying the hADA gene. Subsequently, infected T cells were selected on the basis of their ADA expression, by exposure to a combination of the toxic agent xylofuranosyl‐adenine and the specific ADA inhibitor 2′‐deoxycoformycin. CD4+and CD8+T cells could be infected and selected with equal efficiencies. The genetically modified T cells were shown to contain intact copies of the provirus and to express normal levels of hADA. As expected, uninfected T cells from the ADA‐deficient patient displayed an increased sensitivity to 2′‐deoxyadenosine. Following genetic modification, however, this sensitivity was restored to normal levels in both CD4+and CD8+T cells. The introduction of the hADA gene into the genome of thein vitroexpanded T cells did not alter their phenotype, proliferative capacity or cytotoxic potential. These characteristics were identical to those of T cells derived from healthy individuals. These findings are of critical importance for the clinical application of hADA gene‐tran

ISSN:0014-2980    

DOI:10.1002/eji.1830220111

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY