Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity

Gray, Patrick W.; Aggarwal, Bharat B.; Benton, Charles V.; Bringman, Timothy S.; Henzel, William J.; Jarrett, Julie A.; Leung, David W. M.; Moffat, Barbara; Ng, Peter A.; Svedersky, L P; Palladino, Michael A.; Nedwin, Glenn E.

doi:10.1038/312721a0

Cited by 599 publications

(193 citation statements)

References 48 publications

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“…However, it is unlikely that this interaction plays a role in B cell physiology, as CD160 is not expressed on B cells. Furthermore, the only HVEM binding partner that is present on mature, naive B cells appears to be BTLA (17)(18)(19)(20)(21).…”

Section: Discussionmentioning

confidence: 99%

B and T Lymphocyte Attenuator Regulates B Cell Receptor Signaling by Targeting Syk and BLNK

Vendel¹,

Calemine-Fenaux²,

Izrael-Tomasevic³

et al. 2009

The Journal of Immunology

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B and T lymphocyte attenuator (BTLA) functions as a negative regulator of T cell activation and proliferation. Although the role of BTLA in regulating T cell responses has been characterized, a thorough investigation into the precise molecular mechanisms involved in BTLA-mediated lymphocyte attenuation and, more specifically, its role in regulating B cell activation has not been presented. In this study, we have begun to elucidate the biochemical mechanisms by which BTLA functions to inhibit B cell activation. We describe the cell surface expression of BTLA on various human B cell subsets and confirm its ability to attenuate B cell proliferation upon associating with its known ligand, herpesvirus entry mediator (HVEM). BTLA associates with the BCR and, upon binding to HVEM, recruits the tyrosine phosphatase Src homology 2 domain-containing phosphatase 1 and reduces activation of signaling molecules downstream of the BCR. This is exemplified by a quantifiable decrease in tyrosine phosphorylation of the protein tyrosine kinase Syk, as measured by absolute quantification mass spectrometry. T he B and T lymphocyte attenuator (BTLA) 2 is an Ig superfamily coinhibitory receptor with structural and functional similarities to programmed cell death 1 (PD-1) and CTLA-4 (1-3). However, unlike PD-1 and CTLA-4, which bind members of the B7 Ig superfamily receptors, the established ligand for BTLA is the TNFR family member herpesvirus entry mediator (HVEM) (TNFRSF14) (3-5). HVEM binding leads to tyrosine phosphorylation of the cytoplasmic tail of BTLA, which contains a proposed Grb2/Grb2-related adaptor protein (Grap) docking site and two ITIMs (5-11). Biochemical analysis has revealed that phosphorylation at multiple tyrosines within the cytoplasmic tail of BTLA is necessary and required for efficient recruitment of protein tyrosine phosphatases and BTLA-mediated attenuation of T cell effector response and cell proliferation (5,8,10,11).The role of BTLA appears to be limited to lymphocyte activation as shown in BTLA-deficient mice, which present normal lymphoid organ development and near wild-type lymphocyte numbers. However, these mice display hyperproliferative T and B cell responses to TCR-and BCR-mediated activation, respectively (9, 11). Furthermore, loss of BTLA function leads to increased susceptibility to experimental autoimmune encephalomyelitis and MHC-mismatched allograft rejection, supporting the role of BTLA in modulating T cell activation and effector responses (11,12).Surface expression analysis of BTLA indicates that it is expressed on a wide number of lymphocytes in mice. It is most highly expressed on B cells, followed by CD4 ϩ T cells, and lower expression on CD8 ϩ T cells, macrophages, dendritic cells, and NK cells (9, 13). During murine B cell development, BTLA expression first appears in pre-B cells and shows increased expression through B cell maturation, with the highest expression on mature B cells (9). In this study, we show a detailed cell surface expression profile of BTLA during human B cell deve...

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Section: Discussionmentioning

confidence: 99%

B and T Lymphocyte Attenuator Regulates B Cell Receptor Signaling by Targeting Syk and BLNK

Vendel¹,

Calemine-Fenaux²,

Izrael-Tomasevic³

et al. 2009

The Journal of Immunology

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“…Pure retroviral p24 gag protein was purified from E. coli in a single immunopurification step (Dowbenko et al, 1985) while a five-step process was used to produce human growth hormone (Olsen et al, 1981). Other examples of soluble proteins are human IFN-a (Staehelin et al, 1981;De Maeyer et al, 1982) boVine IFN-a (Grosfeld et al, 1985), chicken triosephosphate isomerase (Straus & Gilbert, 1985), human lymphotoxin (Gray et al, 1984), human TNF (Pennica et al, 1984) and murine TNF .…”

Section: Direct Expressionmentioning

confidence: 99%

The purification of eukaryotic polypeptides synthesized in Escherichia coli

Marston¹

1986

Biochemical Journal

859

379

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“…We examined synovial fluids and sera from 12 patients with RA and 11 patients with reactive arthritis for measurable levels of TNFa, tumor necrosis factor beta (TNFP; lymphotoxin), and gamma-interferon (7-IFN) (5). Our results demonstrate that synovial fluids from RA and reactive arthritis patients differ in content of TNFa and y-IFN.…”

mentioning

confidence: 94%

Detection of tumor necrosis factor α but not tumor necrosis factor β in rheumatoid arthritis synovial fluid and serum

Saxne

Palladino

Talal

et al. 1988

Arthritis & Rheumatism

531

221

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Synovial fluids from 6 of 12 patients with rheumatoid arthritis (RA) and from 3 of 11 patients with reactive arthritis contained measurable levels of tumor necrosis factor α (TNFα). Seven of 12 sera from RA patients contained TNFα, while only 1 of those from reactive arthritis patients was positive. Gamma‐inter‐feron was detected in the synovial fluids and sera of only the RA patients. Tumor necrosis factor β was not detected in any sera or synovial fluids. RA patients with detectable TNFα had higher erythrocyte sedimentation rates and synovial fluid leukocyte counts.

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Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity

Cited by 599 publications

References 48 publications

B and T Lymphocyte Attenuator Regulates B Cell Receptor Signaling by Targeting Syk and BLNK

B and T Lymphocyte Attenuator Regulates B Cell Receptor Signaling by Targeting Syk and BLNK

The purification of eukaryotic polypeptides synthesized in Escherichia coli

Detection of tumor necrosis factor α but not tumor necrosis factor β in rheumatoid arthritis synovial fluid and serum

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