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1. |
Endocytosis of the β chain of interleukin‐2 receptor requires neither interleukin‐2 nor the γ chain |
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European Journal of Immunology,
Volume 24,
Issue 9,
1994,
Page 1951-1955
Agnès Hémar,
Michéle Lieb,
Agathe Subtil,
James P. Disanto,
Alice Dautry‐Varsat,
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摘要:
AbstractInterleukin‐2 (IL‐2) and IL‐2 receptors (IL‐2R) critically regulate the magnitude and duration of T cell expansion required in an immune response. Modulation occurs at the level of receptor number and affinity. IL‐2R is a multisubunit receptor which contains at least three chains, IL‐2Rα (p55), IL‐2Rβ (p70) and IL‐2Rγ (p64). Some components of high‐affinity receptors (αβγ) are continuously internalized in the absence as well as in the presence of IL‐2. From studies on other receptors, it is known that endocytosis of ligand‐receptor complexes is due to an intrinsic property of the receptor. However, the specific chains responsible for endocytosis of high‐affinity IL‐2 receptors have not been fully elucidated. IL‐2Rγ has been reported to be necessary for IL‐2 internalization, based on the fact that fibroblasts transfected with IL‐2Rα and ‐β do not internalize IL‐2. However, IL‐2 dissociates too rapidly from IL‐2Rαβ receptors to allow for its internalization. From the reported results on IL‐2 internalization in transfected fibroblasts, it cannot be concluded as to the respective roles of IL‐2Rβ and/or IL‐2Rγ in endocytosis. As modulation of receptor number is important for biological activity, we have attempted to define the chains responsible for receptor internalization.In this work, we have studied the endocytic properties of IL‐2Rβ. We demonstrate that IL‐2Rβ is constitutively endocytosed in a B cell line, derived from a X‐linked severe combined immunodeficiency patient, which lacks expression of IL‐2Rγ. IL‐2Rβ was also constitutively internalized in T and natural killer cell lines independently of IL‐2Rγ. These results suggest that IL
ISSN:0014-2980
DOI:10.1002/eji.1830240902
出版商:WILEY‐VCH Verlag GmbH
年代:1994
数据来源: WILEY
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2. |
Differences in responsiveness to CD3 stimulation between naive and memory CD4+T cells cannot be overcome by CD28 costimulation |
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European Journal of Immunology,
Volume 24,
Issue 9,
1994,
Page 1956-1960
Heleen Kuiper,
Miranda Brouwer,
Mark de Boer,
Paul Parren,
René A. W. Van Lier,
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摘要:
AbstractActivation of naive CD4+T cells is essential for the induction of primary immune responses. However, this subset is less responsive to signaling via T cell receptor/CD3 (TcR/CD3) complex than memory CD4+cells. For mitogenic activation of T cells, in addition to triggering of the TcR/CD3 complex, costimulatory signals are required that can be generated by surface structures present on the antigen‐presenting cells. We investigated here whether differences in responsiveness to TcR/CD3 stimulation of naive and memory cells can be overcome by the costimulatory pathway B7/CD28. Using a B7‐dependent system we show that even in the presence of optimal CD28 costimulation, CD4+naive cells still have more stringent TcR/CD3 activation requirements than memory cells. Furthermore, titration of the B7 signal revealed that for activation of naive CD4+cells a higher level of cross‐linking of CD28 molecules is required than for memory cells. Thus, our results show that at least two signals are required for activation of both CD4+memory and naive cells, but that for activation of naive cells higher cross‐linking of both CD3 and CD28 molecules is ne
ISSN:0014-2980
DOI:10.1002/eji.1830240903
出版商:WILEY‐VCH Verlag GmbH
年代:1994
数据来源: WILEY
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3. |
The gold anti‐rheumatic drug auranofin governs T cell activation by enhancing oxygen free radical production |
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European Journal of Immunology,
Volume 24,
Issue 9,
1994,
Page 1961-1965
Irene A. M. Vint,
John C. Foreman,
Benjamin M. Chain,
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摘要:
AbstractGold‐containing drugs continue to be used in the treatment of rheumatoid arthritis, but their mode of action remains unknown. One model to explain gold action is that gold‐containing compounds can alter free radical production in cells of the immune system, but direct evidence for this hypothesis has been lacking. In this study we show that auranofin can enhance the rapid flux of reactive oxygen species (ROS), which accompanies phytohemagglutinin activation of peripheral blood T cells. Blocking this enhancement by the addition of antioxidants can reverse the functional effects of the drug on T cell responses, which we have previously demonstrated. These results provide strong experimental support for a model in which gold anti‐rheumatics act by modulating ROS production. Furthermore, our experiments suggest that auranofin may be a useful tool to investigate the postulated role of ROS in the intra cellular T cell signaling pa
ISSN:0014-2980
DOI:10.1002/eji.1830240904
出版商:WILEY‐VCH Verlag GmbH
年代:1994
数据来源: WILEY
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4. |
Defective lymphokine production by most CD8+and CD4+tumor‐specific T cell clones derived from human melanoma‐infiltrating lymphocytes in response to autologous tumor cellsin vitro |
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European Journal of Immunology,
Volume 24,
Issue 9,
1994,
Page 1966-1973
Yannick Guilloux,
Christophe Viret,
Nadine Gervois,
Eric Le Dréan,
Marie‐Christine Pandolfino,
Elisabeth Diez,
Francine Jotereau,
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摘要:
AbstractHuman melanomas are infiltrated by tumor‐reactive T lymphocytes. However, the ability of these cells to elicit a specific anti‐tumor responsein vivoremains to be established. Because lymphokine production is critical for T cell functions, we have analyzed the capacity of melanoma‐specific tumor‐infiltrating lymphocyte (TIL) clones to produce major lymphokines: interleukin‐2 (IL‐2), interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4), as well as tumor necrosis factor (TNF), in response to direct antigen presentation by autologous and allogeneic tumor cells. We report here that, upon stimulation by autologous melanoma cells, all TIL clones secreted TNF but only a few of them produced significant amounts of IL‐2, IL‐4 or IFN‐γ. Nonetheless, all these clones consistently produced two or three of these last lymphokines upon stimulation with phorbol myristate acetate and calcium ionophore, as well as IL‐2 upon CD3 stimulation, showing the existence of three lymphokine profiles among them: Th1, Th0 and a profile characterized by IL‐2 and IL‐4, but not IFN‐γ secretion. Stimulation of TIL clones by allogeneic melanoma lines sharing the appropriate HLA‐peptide complexes revealed that defective IL‐2 production seemed to be a constant feature for some clones, while it was, for other clones, dependent on the antigen‐presenting tumor cells. For this last type of clone, we further showed that defective IL‐2 induction resulted from an LFA‐3 defect of some melanoma cells or from distinct yet undefined defects of other melanoma lines. Our data suggest that defective lymphokine secretion may be an essential component of thein vivofailure of melanoma‐reactive TIL to control tumor development. Interestingly both CD4+and CD8+TIL clones from one patient were fully activated by the autologous melanoma cellsin vitro, supporting a potential role of s
ISSN:0014-2980
DOI:10.1002/eji.1830240905
出版商:WILEY‐VCH Verlag GmbH
年代:1994
数据来源: WILEY
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5. |
In vivotolerization of Th1 lymphocytes following a single feeding with ovalbumin: Anergy in the absence of suppression |
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European Journal of Immunology,
Volume 24,
Issue 9,
1994,
Page 1974-1981
Doron Melamed,
Aharon Friedman,
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摘要:
AbstractOral tolerance is a biologically relevant pathway for inducing peripheral tolerance to foreign antigens. The mechanisms responsible for the tolerant state following feeding with antigen have been shown to involve both anergy and suppression. The demonstration of anergic T lymphocytes following oral tolerance has so far been limited inin vitrosystems, and a primary objective of the present study was to provide evidence,in vivo, for the existence of a state of anergy in mice orally fed with ovalbumin (OVA). In addition, it has been shown that peripheral anergy following the intravenous administration of antigen is selectively induced in Th1 lymphocytes. Thus, a second objective of this study was to investigate whether tolerance induced by a feeding regimen known to cause anergy could be selectively limited to Th1 lymphocytes, and whether tolerance induction could be explained by antigen absorption from the gut into the circulation. Oral tolerance was induced by a single feeding with OVA, and was demonstrated by diminished antibody productionin vivo, and by reduced cytokine secretion or proliferationin vitro.Anergy, as a mechanism for tolerance, was demonstrated by the ability to reverse the tolerant state after culturing tolerant cells in recombinant interleukin‐2 (rIL‐2). Reversal of the tolerant statein vivowas established by antibody production in irradiated mice adoptively transferred with cells cultured in the presence of rIL‐2. The possibility that suppression was also anin vivomechanism for tolerance was studied by adoptive transfer experiments. Our results show: 1) that a single dose of orally administered OVA leads to the selective tolerization of Th1 responses (diminished IgG2a, IL‐2 and interferon‐γ production) with intact Th2 responses (IgG1, and IL‐4), 2) that tolerancein vivois explained by anergy in the absence of active suppression, 3) that exposure of tolerant cells to rIL‐2in vitroabrogates the anergic state bothin vitro(proliferation and cytokine secretion) andin vivo(IgG2a production), and 4) that the induction of oral tolerance is inhibited by the presence of antibodies specific for the tolerizing antigen. These findings indicate that the induction of anergy via the oral route might depend on the dissemination of antigen absorbed from the gut. It is suggested that tolerance is guaranteed by the fact that this absorbed antigen is presented to Th1 lymphocytes in the absence of inflammatory and co‐stimulatory molecules; these foreign antigens are thus not different fr
ISSN:0014-2980
DOI:10.1002/eji.1830240906
出版商:WILEY‐VCH Verlag GmbH
年代:1994
数据来源: WILEY
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6. |
Evidence for a selective and multi‐step model of T cell differentiation: CD4+CD8lowthymocytes selected by a transgenic T cell receptor on major histocompatibility complex class I molecules |
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European Journal of Immunology,
Volume 24,
Issue 9,
1994,
Page 1982-1987
Hanspeter Pircher,
Pamela S. Ohashi,
Richard L. Boyd,
Hans Hengartner,
Karin Brduscha,
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摘要:
AbstractWe have characterized a prominent (15‐20 %) thymocyte population expressing CD4 at a high and CD8 at a low level “CD4+8lo” in mice transgenic for a T cell receptor “TCR” restricted by major histocompatibility complex “MHC” class I molecules. The results demonstrate that the CD4+8lopopulation is an intermediate stage between immature CD4+8+and end‐stage CD4+8‐thymocytes and that the survival of these cells crucially depends on the successful interaction of the transgenic TCR with self MHC class I molecules. In addition we demonstrate that the avidity of the interaction between TCR and self MHC class I molecules determines whether CD4+8lothymocytes are found in significant numbers in this transgenic model. Our findings support a selective and multi‐step model of T cell differenti
ISSN:0014-2980
DOI:10.1002/eji.1830240907
出版商:WILEY‐VCH Verlag GmbH
年代:1994
数据来源: WILEY
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7. |
Unconventional cytotoxic T lymphocyte recognition of synthetic peptides corresponding to residues 1—23 of Ras protein |
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European Journal of Immunology,
Volume 24,
Issue 9,
1994,
Page 1988-1992
Li Yin,
Claire Thomas,
J. Justin Hsuan,
Hans J. Stauss,
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摘要:
AbstractA peptide corresponding to amino acids 1 through 23 of Ras protein containing a mutation at position 12 was used to induce cytotoxic T lymphocytes (CTL) in mice. Although the CTL were CD8+and expressed α, β T cell antigen receptors (TCR), their major histocompatibility complex (MHC)‐restriction was unconventional. They recognized peptide‐treated murine cells of different H‐2 haplotypes, but not MHC class I‐negative cells. Human HLA class I molecules did not present Ras peptides and hybrid human/mouse MHC molecules revealed that all three extracellular domains α1, α2 and α3 were required for recognition by peptide‐specific CTL. Shortening the 23‐mer peptide by 5 residues at either the amino or carboxy terminus resulted in loss of CTL recognition. This demonstrates an unusual form of antigen recognition by mouse CTL in which peptide presentation requires murine H‐2 class I molecules but is not class I allele restricted, and the peptides recognized are much larger than peptides in conventional class I‐
ISSN:0014-2980
DOI:10.1002/eji.1830240908
出版商:WILEY‐VCH Verlag GmbH
年代:1994
数据来源: WILEY
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8. |
Signaling properties of anti‐immunoglobulin — resistant variants of WEHI‐231 B lymphoma cells |
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European Journal of Immunology,
Volume 24,
Issue 9,
1994,
Page 1993-1999
Laure E. Benhamou,
Takeshi Watanabe,
Daisuke Kitamura,
Pierre‐André Cazenave,
Pierre Sarthou,
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摘要:
AbstractStimulation of the B cell antigen receptor (BCR) of the murine immature WEHI‐231 B lymphoma with anti‐immunoglobulin antibodies leads to irreversible growth arrest and apoptosis. As in normal B cells, membrane immunoglobulin (mIg) ligation in WEHI‐231 cells triggers a series of signaling cascades from the BCR to intracellular compartments. In order to address the role of early signals in mediating the growth arrest of WEHI‐231 cells, we have generated two variants resistant to the anti‐Ig‐mediated inhibitory effect. Some of the properties of these variants have been recently described in terms ofbcl‐2andc‐mycgene regulation. We report here that these variants can be further distinguished from the wild type on the basis of significant alterations in the early biochemical events which follow mIg ligation. Both Ca2+signals and patterns of protein tyrosine phosphorylation were affected in these variants, suggesting that alterations in the early signal transduction machinery may have profound effects on the fate of B cells. In addition, we found that expression of the p75HSIsubstrate of p53/56lynwas strikingly reduced in both variants as compared to the wild type. These findings support the view that p75HSImay play a critical role in BCR‐dependent s
ISSN:0014-2980
DOI:10.1002/eji.1830240909
出版商:WILEY‐VCH Verlag GmbH
年代:1994
数据来源: WILEY
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9. |
Identification of collagen and laminin receptor integrins on murine T lymphocytes |
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European Journal of Immunology,
Volume 24,
Issue 9,
1994,
Page 2000-2005
Sachiko Miyake,
Tomoko Sakurai,
Ko Okumura,
Hideo Yagita,
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摘要:
AbstractIn this study we investigated the receptors by which murine lymphocytes bind to collagen and laminin. To identify the collagen and laminin receptors, we generated three monoclonal antibodies, two of which (HMα1 and HMα2) could inhibit adhesion of activated T cells to collagen and laminin and one of which (HMα6) could inhibit that to laminin. Biochemical studies showed that the antigens recognized by HMα1, HMα2, and HMα6 are the mouse homologues of human VLA‐1, VLA‐2, and VLA‐6, respectively. Finally, we demonstrated that both VLA‐1 and VLA‐2 contribute to the functional interaction between collagen and activated T cells, since HMα1 and HMα2 specifically inhibited collagen‐induced TNF secretion from activated T cells. These results indicate that VLA‐1 and VLA‐2 play an important role in regulating adhesion and cytokine producti
ISSN:0014-2980
DOI:10.1002/eji.1830240910
出版商:WILEY‐VCH Verlag GmbH
年代:1994
数据来源: WILEY
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10. |
The two soluble forms of the lipopolysaccharide receptor, CD14: Characterization and release by normal human monocytes |
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European Journal of Immunology,
Volume 24,
Issue 9,
1994,
Page 2006-2012
Jean‐Jacques Durieux,
Natalio Vita,
Octavian Popescu,
Frederique Guette,
Julia Calzada‐Wack,
Reinhold Munker,
Reinhold E. Schmidt,
Jan Lupker,
Pascual Ferrara,
H. W. Löms Ziegler‐Heitbrock,
Mario O. Labeta,
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摘要:
AbstractCD14, a glycolipid‐anchored membrane glycoprotein, acts as a high affinity lipopolysaccharide receptor on leukocytes. We previously reported that the Mono‐Mac‐6 cell line releases two different soluble forms of CD14 (sCD14) (Labeta et al.Eur. J. Immunol.1993.23: 2144). Here we show that the two sCD 14, which we now refer to as sCD 14α (low Mr), and sCD 14β (high Mr), are also synthesized and released by normal human monocytes and present in normal plasma. Their mechanism of release was examined by using the Mono‐Mac‐6 cell line, chinese hamster ovary cell (CHO)/CD14+transfectants and plasma from paroxysmal nocturnal hemoglobinuria (PNH) patients. It was found that: (1) sCD14β is released faster than sCD 14α and that the release of the latter is a lengthy process. (2) Monensin blocked the biosynthesis of membrane‐bound CD14 (mCD 14) and sCD 14, additionally, a 50‐kDa CD14 polypeptide accumulated in the cell lysate, suggesting that the different forms of CD14 may have a common precursor. (3) Monensin also blocked the release of mCD14α from surface‐labeled cells, suggesting that conversion of mCD14 to sCD14α involves a mechanism of endocytosis followed by exocytosis. Interestingly, (4) sCD 14α and sCD 14β were detected in PNH plasma, indicating that sCD14α may also derive from an endogenous pathway. (5) Phospholipase C‐released CD 14 was identical in size to mCD 14, thus differed from sCD 14β by ˜ 2000, indicating that release of sCD 14β involves further processing. (6) CHO cells transfected with a CD14 cDNA coding for an eight C‐terminal amino acids shorter product released an sCD 14β‐like form; thus absence of the eight C‐terminal amino acids prevented mCD 14 expression but not the secretion of sCD 14β. The characterization of sCD 14α and sCD 14β reported here may be useful for better understanding of variations in sCD 14 levels in pathological conditions and the contribution of each sCD 14 in scp
ISSN:0014-2980
DOI:10.1002/eji.1830240911
出版商:WILEY‐VCH Verlag GmbH
年代:1994
数据来源: WILEY
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