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1. |
Reduced production of interleukin 2 and interferongamma and enhanced helper activity for IgG synthesis by cloned CD4+T cells from patients with AIDS |
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European Journal of Immunology,
Volume 17,
Issue 12,
1987,
Page 1685-1690
Enrico Maggi,
Donatella Macchia,
Paola Parronchi,
Marcello Mazzetti,
Adriana Ravina,
Domenico Milo,
Sergio Romagnani,
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摘要:
AbstractPurified T lymphocytes (E rosetting cells) isolated from peripheral blood (PB) of four patients with acquired immune deficiency syndrome (AIDS) were cloned under culture conditions (phytohemagglutinin plus interleukin 2) which allow clonal expansion of most T lymphocytes. A total number of 101 T cell clones (37 CD4+and 64 CD8+) from PB of AIDS patients and of 188 T cell clones (115 CD4+and 73 CD8+) from PB of four normal controls were obtained and tested for their helper function as well as for their capacity to release lymphokines. Unstimulated CD4+TCC from patients with AIDS showed enhanced helper function for IgG synthesisin vitroin both autologous and normal allogeneic B cells in comparison to clonable CD4+T cells of normal donors. Such activity was further potentiated by addition to the cell cultures of anti‐CD3 monoclonal antibody. The majority of CD4+T cell clones from AIDS patients showed a reduced ability to produce interleukin 2 and interferon‐γ in response to activation with phytohemagglutinin. However, most of them released greater amounts of soluble factor(s) able to promote B cell proliferation of anti‐IgM‐activated normal B cells and to induce the differentiation of normal B lymphocytes into IgG‐secreting cells.These data demonstrate that most surviving CD4+T cells in PB of patients with AIDS belong to a T cell subset producing B cell growth and differentiation factors, which may contribute to the B cell hyperactivation seen in AID
ISSN:0014-2980
DOI:10.1002/eji.1830171202
出版商:WILEY‐VCH Verlag GmbH
年代:1987
数据来源: WILEY
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2. |
Rapid decrease in lymphocyte adherence to high endothelial venules in lymph nodes deprived of afferent lymphatic vessels |
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European Journal of Immunology,
Volume 17,
Issue 12,
1987,
Page 1691-1695
Hans R. Hendriks,
Adrian M. Duijvestijn,
Georg Kraal,
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摘要:
AbstractOcclusion of the afferent lymph flow to the lymph node (LN) results in both flattening of the endothelium of high endothelial venules (HEV) and a severe decrease in numbers of lymphocytes in transit across the walls of the flattened HEV. In the present study we have used thein vitrolymphocyte‐binding assay to investigate the ability of HEV in rat LN to bind lymphocytes at various time points after occlusion of the afferent lymph flow. In addition the specificity of T and B lymphocyte adherence to HEV of such operated LN was studied.In normal LN, lymphocytes adhered to virtually all HEV using thein vitrobinding assay. However, 1 and 2 weeks after operation lymphocytes bound to only 50–60% of the HEV and by 3–6 weeks 20–30%. The total numbers of lymphocytes bound to these HEV had also diminished to 10% of the control value 3–6 weeks after operation. Morphometric analysis showed that this was not only due to a reduction in the area of HEV endothelium available for lymphocyte adherence by flattening of the high endothelial cells, but also to a strong decrease in the numbers of bound lymphocytes per unit area high endothelium. In spite of the reduction in numbers of adhering lymphocytes the T/B cell ratio did not change. The results show that the reduction in lymphocyte binding of HEV in operated LN is a rapid event, probably due to loss of high endothelial cell determinants involved in binding of lymphocytes. The decrease in lymphocyte binding clearly precedes flattening of HEV endothelium suggesting that the height of high endothelial cells is of secondary importance to lymphocyte
ISSN:0014-2980
DOI:10.1002/eji.1830171203
出版商:WILEY‐VCH Verlag GmbH
年代:1987
数据来源: WILEY
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3. |
T lymphocyte recognition of acetylcholine receptor: Localization of the full T cell recognition profile on the extracellular part of the α chain ofTorpedo californicaacetylcholine receptor |
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European Journal of Immunology,
Volume 17,
Issue 12,
1987,
Page 1697-1702
Tsuyoshi Yokoi,
Biserka Mulac‐Jeričević,
Jun‐Ichi Kurisaki,
M. Zouhair Atassi,
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摘要:
AbstractA series of eighteen consecutive overlapping synthetic peptides, of uniform size and overlaps, which encompass the entire extracellular part (residues 1–210) of theTorpedo californicaacetylcholine receptor α chain were examinedin vitrofor their ability to stimulate lymph node cells from acetylcholine receptor‐primed C57BL/6 (H‐2b), C3H/He (H‐2k), SWR (H‐2q) and SJL (H‐2s) mice. The recognition sites (T sites) by acetylcholine receptor‐primed lymph node cells from these mouse strains resided within six regions on the extracellular part of the α chain. Three of the regions recognized by T cells conincided with regions recognized by antibodies (i.e.B cells) and one of these three regions also coincided with an a‐neurotoxin‐binding region. It is noteworthy that, in addition to sites recognized by both T and B cells, the protein has at least two sites which are recognized exclusively by T cells and to which no detectable antibody res
ISSN:0014-2980
DOI:10.1002/eji.1830171204
出版商:WILEY‐VCH Verlag GmbH
年代:1987
数据来源: WILEY
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4. |
Bovine cytotoxic T cell clones which recognize lymphoblasts infected with two antigenically different stocks of the protozoan parasiteTheileria parva |
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European Journal of Immunology,
Volume 17,
Issue 12,
1987,
Page 1703-1709
W. Ivan Morrison,
Bruno M. Goddeeris,
Alan J. Teale,
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摘要:
AbstractThe Muguga and Marikebuni stocks ofTheileria parvadiffer on the basis of cross‐protection and in their schizont antigen profile determined with a panel of parasitespecific monoclonal antibodies. The phenotype and specificity of six cytotoxic T cell clones generated from an animal immunized againstT. parva(Marikebuni) were investigated. All six clones had the BoT2+BoT4−BoT8+phenotype, were dependent on both specific antigen and T cell growth factor for proliferation and were restricted by determinants on class I major histocompatibility complex molecules. The clones killed target cells infected with either the Muguga or Marikebuni stocks of the parasite; the target cell lines tested included T cell clones which were infectedin vitrowith the two parasite stocks and subsequently recloned. The specificity of these cytotoxic T cell clones contrasts with that of T cell clones generated previously from animals immunized againstT. parva(Muguga), in that the latter were specific for target cells infected with the Muguga stock of the parasite. Moreover, one of the clones generated againstT. parva(Marikebuni) was restricted by the same major histocompatibility complex molecule as the Muguga‐specific T cell clones. The difference in parasite strain‐specificity between the two sets of clones appears to reflect the capacities of the two parasite stocks to cross‐protect, since animals immunized againstT. parva(Marikebuni) are protected against challenge withT. parva(Muguga) whereas a proportion of animals immunized withT. parva(Muguga) are susceptible to challenge withT. parva(Marikebuni). Another difference between the two sets of T cell clones was that those generated againstT. parva(Marikebuni) only killed a proportion of cells of a given cell line in a 4‐h cytotoxicity assay, whereas Muguga‐specific T cells invariably kill the majority of cells. However, despite this partial killing, the clones markedly inhibited growth of parasitized cell lines when cultured with them for a per
ISSN:0014-2980
DOI:10.1002/eji.1830171205
出版商:WILEY‐VCH Verlag GmbH
年代:1987
数据来源: WILEY
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5. |
Activation of murine CD8+lymphocytes: Two distinct signals regulatec‐mycand interleukin 2 receptor RNA expression |
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European Journal of Immunology,
Volume 17,
Issue 12,
1987,
Page 1711-1717
Conny Hardt,
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摘要:
AbstractResting cytotoxic T lymphocyte precursors (CTL‐P; CD8+) constitutively express T cell receptors (TcR) on their cell surfaces. CTL‐P are preactivated if binding of the corresponding antigen (mitogens, allogeneic major histocompatibility complex (MHC) determinants, viral proteins or haptens in conjunction with self MHC structures) to the TcR takes place. Using amycspecific probe I show that within 12 h antigen binding leads to optimalc‐mycRNA expression which seems to be the first sign that resting CTL‐P are preactivated. Thereafter,c‐mycRNA expression was remarkably reduced only at day 5. Antigen alone, however, is not sufficient for interleukin 2 receptor (IL 2R) RNA expression. A monocyte‐derived, soluble mediator termed IL 2R‐inducing factor (RIF) acts in conjunction with antigen to induce the expression of IL 2R RNA and functional IL 2R on the cell surface. RIF is a 44‐kDa heat‐labile protein produced by accessory cells and its function is restricted to CD8+lymphocytes. IL 2R RNA is first expressed 12 h after onset of culture, maximally expressed on day 3 and it decreases thereafter. Cells kept in long‐term culture without mitogen but in the presence of IL 2 do not express high amounts of IL 2R RNA. Expression of IL 2R RNA can be very efficiently reinduced, however, by mitogenic stimulation. In contrast to primary cultures, IL 2R RNA expression peaks earlier and is independent of RIF. The results obtained here show that (a) for CD8+lymphocytes of primary cultures two distinct activation signals (mitogen and RIF) are necessary forc‐mycand IL 2R RNA expression and (b) for CD8+lymphocytes of secondary cultures the mitogenic signal alone is sufficient for re‐
ISSN:0014-2980
DOI:10.1002/eji.1830171206
出版商:WILEY‐VCH Verlag GmbH
年代:1987
数据来源: WILEY
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6. |
Two types of gamma T cell receptors expressed by T cell acute lymphoblastic leukemias |
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European Journal of Immunology,
Volume 17,
Issue 12,
1987,
Page 1719-1728
Jacques J. M. van Dongen,
Ingrid L. M. Wolvers‐Tettero,
J. G. Seidman,
Siew‐Lan Ang,
René J. van de Griend,
Evert F. R. De Vries,
Jannie Borst,
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摘要:
AbstractCD3+cells, isolated from peripheral blood of two patients with T cell acute lymphoblastic leukemia (T‐ALL), did not react with the monoclonal antibody WT31, which is thought to recognize a framework determinant on the conventional T cell receptor (TcR), consisting of disulfide‐linked α and β chains. The T‐ALL cells of neither patient synthesized TcRα mRNA; the cells of patient DD contained only truncated (D‐J) TcRβ mRNA, while the cells of patient HZ contained truncated as well as mature (V‐D‐J) TcRβ mRNA. The leukemic cells of both patients made TcRγ mRNA. At the cell surface, the T‐ALL cells of patient DD expressed a CD3‐associated disulfide‐linked dimer, which contained the TcRγ protein. On the leukemic cells of patient HZ the TcRγ protein was present as a 41‐44‐kDa CD3‐associated subunit in a noncovalently linked form. The TcRγ genes in the T‐ALL cells of patient DD were rearranged exclusively to the Cγ1 locus, while in the T‐ALL cells of patient HZ both Cγ1 alleles were deleted and rearrangement to the Cγ2 locus had occurred. The Cγ1 gene segment, just like the TcRα and TcRβ gene segments, contains a cysteine codon in its second exon. This cysteine residue is involved in the formation of the interchain disulfide bond. The human Cγ2 gene segment, however, does not contain a cysteine codon in its second exon. The absence of the cysteine residue in Cγ2 encoded TcRγ chains explains the lack of an interchain disulfide bond in the TcR on the T‐ALL cells of patient HZ. The TcR gene configuration, as well as the expression of TcR mRNA and TcR protein as observed in these two leukemias, is consistent with a model for T cell differentiation in which the TcRγ gene rearranges first to the Cγ1 locus prior to or coinciding with D‐J joining of the TcRβ gene, followed by rearrangement
ISSN:0014-2980
DOI:10.1002/eji.1830171207
出版商:WILEY‐VCH Verlag GmbH
年代:1987
数据来源: WILEY
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7. |
Unusual forms of T cell γ mRNA in a human T cell leukemia cell line: Implications for γ gene expression |
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European Journal of Immunology,
Volume 17,
Issue 12,
1987,
Page 1729-1736
Lynette Tighe,
Alan Forster,
David M. Clark,
Arthur W. Boylston,
Isabella Lavenir,
Terence H. Rabbitts,
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摘要:
AbstractThe expression and rearrangement of T cell rearranging (TRG) γ genes in human leukemic cell lines has been examined. The cell line MOLT‐17 produces abundant γ mRNA which is translated into a protein found on the cell surface which is associated with the CD3 molecule. The analysis of the γ mRNA sequences in MOLT‐17, by cDNA cloning, shows transcripts of aberrantly rearranged genes as well as the productively rearranged allele. The productive allele consists of a rearranged V 8 gene joined to Jγ2. Two forms of aberrant transcript originate from the other rearranged γ allele. One of these initiates just upstream of the unrearranged Jγ2 segment, and the other initiates from a Vγ8 gene segment joined to another Jγsegment, upstream of Jγ2. An unusual feature of the latter transcript is that polyadenlyation has occurred at the end of the first exon of Cγ2, where two conserved poly(A) addition signals occur. The MOLT‐4 cell line, on the other hand, has productively and nonproductively rearranged γ alleles, from which relatively little transcription occurs. These results define new Jγsegments in the human TRG γ locus and suggest that positive activation of the γ locus is necessary for high level transcription
ISSN:0014-2980
DOI:10.1002/eji.1830171208
出版商:WILEY‐VCH Verlag GmbH
年代:1987
数据来源: WILEY
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8. |
Response of human B cells to different anti‐immunoglobulin isotypes: Absence of a correlation between early activation events and cell proliferation |
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European Journal of Immunology,
Volume 17,
Issue 12,
1987,
Page 1737-1742
Chaim M. Roifman,
Gordon B. Mills,
David Stewart,
Roy K. Cheung,
Sergio Grinstein,
Erwin W. Gelfand,
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摘要:
AbstractCross‐linking of surface immunoglobulin (sIg) by antibodies against IgM, IgG and IgD activates B cells and in some circumstances can induce cell proliferation. We studied the potential link between anti‐Ig‐induced changes in the cytosolic free Ca2+concentration ([Ca2+]i), inositol phosphate production and the ability to induce cell proliferation in the presence or absence of the phorbol ester 12‐O‐tetradecanoylphorbol 13‐acetete (TPA). Anti‐IgM, but not anti‐IgD or anti‐IgG, induced cell proliferation in the presence but not the absence of TPA. Each of the antibodies induced a rapid increase in [Ca2+]iwhich appeared to be due to release of Ca2+from internal stores. This was followed by a sustained increase in [Ca2+]i, apparently due to Ca2+uptake from the extracellular medium. Anti‐IgD induced the greatest increase in [Ca2+]i, anti‐IgM induced intermediate changes and anti‐IgG the lowest change. Since inositol 1,3,5‐trisphosphate (IP3) can release Ca2+from internal stores, we tested the ability of each anti‐Ig isotype to increase concentrations of IP3.In contrast to the change in [Ca2+]iand proliferation, anti‐IgG induced the most significant increase in IP3concentrations. Taken together these data indicate that changes in [Ca2+]i, inositol phosphate production and anti‐Ig‐induced human B cell proliferation are not directly linked. They also demonstrate that changes in [Ca2+]i, inositol phosphate production and activation of protein kinase C are not sufficient to induce proliferation of human B cells. It appears that anti‐IgM induces an additional Ca2+‐independent, inositol phosphate‐independent and protein kinase C‐independent activation signal which can collaborate with TPA to induce B cell proliferation. The molecular events involv
ISSN:0014-2980
DOI:10.1002/eji.1830171209
出版商:WILEY‐VCH Verlag GmbH
年代:1987
数据来源: WILEY
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9. |
Recombinant human interleukin 5 is an eosinophil differentiation factor but has no activity in standard human B cell growth factor assays |
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European Journal of Immunology,
Volume 17,
Issue 12,
1987,
Page 1743-1750
Elaine Clutterbuck,
John G. Shields,
John Gordon,
Susan H. Smith,
Andrew Boyd,
Robin E. Callard,
Hugh D. Campbell,
Ian G. Young,
Colin J. Sanderson,
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摘要:
AbstractFollowing the observation that mouse interleukin 5 (IL 5) is active as a B cell growth factor (BCGF) as well as an eosinophil differentiation factor, this work was carried out to test recombinant human IL 5 for BCGF activity. A highly active, partially purified batch of recombinant human IL 5 was prepared and tested for BCGF activity in four laboratories. This batch gave a 50% endpoint of 1:77450 in the human eosinophil differentiation assay, 1:983 in the mouse eosinophil differentiation assay and 1:42 in the mouse BCL1assay, thus demonstrating that, like mouse IL 5, human IL 5 has cross‐species activity. By comparison with the assays in the mouse this batch would be expected to have 50% maximal human BCGF activity of about 1:4000. In each assay a known positive factor was used as a positive control, and there was no inhibitory activity in the preparation. However, despite the activity towards the mouse B cell lymphoma, the results showed no detectable activity in a panel of assays used to identify human BCGF and B cell differentiation factors. These assays included (a) proliferation assays with tonsillar or splenic B cells in the presence of the co‐stimulators anti‐μ or phorbol myristate acetate; (b) a restimulation assay in which tonsillar B cells are first activated with eitherStaphylococcus aureusCowan 1 or a mixture of phorbol dibutyrate and ionomycin, or splenic B cells are first activated with anti‐μ; (c) production of immunoglobulin by B cells in a restimulation assay withStaphylococcus aureusCowan 1; (d) production of immunoglobulin by the Epstein‐Barr virus‐transformed B lymphoblastoid CESS cell line; (e) the ability to stimulate proliferation of chronic lymphocytic leukemia (B‐CLL) cells freshly explanted from three different patients; (f) the ability to stimulate the B lymphoma (L4) cell line and the mature B cell (HBF1) line, and (g) the ability to replace T cells in specific antibody responses.It therefore seems unlikely that recombinant human IL 5 is either a growth or a differentiation factor for human B cells, and raises the interesting question of the biological significance of the BCGF activity of this fact
ISSN:0014-2980
DOI:10.1002/eji.1830171210
出版商:WILEY‐VCH Verlag GmbH
年代:1987
数据来源: WILEY
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10. |
Abrogation of the lethal graft‐vs.‐host reaction developed to non‐H‐2 antigens: involvement of T suppressor cells distinct from veto cells |
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European Journal of Immunology,
Volume 17,
Issue 12,
1987,
Page 1751-1755
Olga Halle‐Pannenko,
Linda L. Pritchard,
Martine Bruley‐Rosset,
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摘要:
AbstractThe mortality induced by graft‐vs.‐host reaction (GVHR) in (DBA/2 × B10.D2)F1recipients transplanted with cells from H‐2d‐identical B10.D2 donors can be abrogated by preimmunizing the donors with parent‐strain spleen cells from normal DBA/2 mice. The experiments described here were designed to explore the possibility that the observed protection might be mediated by veto cells contained in the immunizing cell inoculum; the reasoning was based on an analogy with the cytotoxic T lymphocyte response to non‐H‐2 antigens where suppression can be mediated by veto cells, present in the spleens of normal mice, which are radiosensitive and largely Lyt‐2+. We show that the intensity of the protection against GVHR mortality is a function of the immunizing cell dose, and that protection remains effective when optimal doses of immunizing cells are (a) irradiated or (b) pretreated with anti‐Thy‐1 serum. GVHR suppression is abrogated when, before transfer to F1recipients, suppressor cells from spleens of immunized donors are pretreated with antiserum directed against Lyt‐1.2 (expressed by B10.D2 but not by DBA/2, which expresses Lyt‐1.1); in contrast, it is not significantly affected when these same cells are pretreated with anti‐Lyt‐2.2 alloantiserum. We conclude that when the antigen load is great enough the immunizing cells play a largely passive role in the observed suppression. The protection against GVHR mortality seen in this H‐2‐compatible combination is transferable by Lyt‐1+2−suppressor T cells originating in mice given high doses of alloantigen. These suppressor cells are therefore distinct from the splenic veto T cells effective against cytotoxic T lymphocyte responses to non‐H‐2 antigens. The mechanism of the observed suppression and its rela
ISSN:0014-2980
DOI:10.1002/eji.1830171211
出版商:WILEY‐VCH Verlag GmbH
年代:1987
数据来源: WILEY
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