In attempt to elucidate the mechanism of the HIV infection induced T cell unresponsiveness, we studied signal-transducing molecules proximal to the T cell receptor (TCR) in T lymphocytes of HIV-infected individuals. Total amounts of protein tyrosine kinases (PTKs) Lck, Fyn, and ZAP-70 and the zeta chain of the TCR were found significantly decreased in T cells of symptomatic/AIDS patients as well as in T cells of individuals in acute and early asymptomatic stages of HIV infection. Unexpectedly, the detection of Lck, Fyn, and ZAP-70 was reversed after the treatment of cell lysates with dithiothreitol. This suggests that PTKs Lck, Fyn, and ZAP-70 were modified by a mechanism altering the status of sulfhydryl groups. Moreover, this mechanism seems to affect selectively T cells of HIV infected patients since B cell PTKs Syk and Lyn were detected structurally and functionally intact. Interestingly, similar alterations of signaling molecules were not detected in T cells of HIV-infected long-term asymptomatic individuals. Modification of T cell PTKs may thus underlie the HIV-induced impairment of lymphocyte function and may potentially predict disease progression.
I Stefanová, M W Saville, C Peters, F R Cleghorn, D Schwartz, D J Venzon, K J Weinhold, N Jack, C Bartholomew, W A Blattner, R Yarchoan, J B Bolen, I D Horak
Title and authors | Publication | Year |
---|---|---|
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MT Pinto, TM Malta, ES Rodrigues, OM Takayanagui, Y Tanaka, DT Covas, S Kashima |
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GM Deng, J Beltran, C Chen, C Terhorst, GC Tsokos |
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Transactions of the American Clinical and Climatological Association | 2013 |
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ER Mann, NE McCarthy, ST Peake, AN Milestone, HO Al-Hassi, D Bernardo, CT Tee, J Landy, MC Pitcher, SA Cochrane, AL Hart, AJ Stagg, SC Knight |
Clinical & Experimental Immunology | 2012 |
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A Rizvi, MJ Pecaut, JM Slater, S Subramaniam, DS Gridley |
International Journal of Radiation Biology | 2011 |
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S Gelkop, B Weisman, RN Pulak, D Zharhary, N Isakov |
Journal of Immunological Methods | 2011 |
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R Potula, BJ Hawkins, JM Cenna, S Fan, H Dykstra, SH Ramirez, B Morsey, MR Brodie, Y Persidsky |
Journal of immunology (Baltimore, Md. : 1950) | 2010 |
Topley & Wilson's Microbiology and Microbial Infections
PM Pitha, MS Künzi |
Topley & Wilson's Microbiology and Microbial Infections | 2010 |
Phenotypic and functional characterization of a mouse model of targeted Pig-a deletion in hematopoietic cells
V Visconte, N Raghavachari, D Liu, K Keyvanfar, MJ Desierto, J Chen, NS Young |
Haematologica | 2009 |
Regulatory activity of azabisphosphonate-capped dendrimers on human CD4+ T cell proliferation enhances ex-vivo expansion of NK cells from PBMCs for immunotherapy
D Portevin, M Poupot, O Rolland, CO Turrin, JJ Fournié, JP Majoral, AM Caminade, R Poupot |
Journal of Translational Medicine | 2009 |
Regulatory activity of azabisphosphonate-capped dendrimers on human CD4+ T cell proliferation enhances ex-vivo expansion of NK cells from PBMCs for immunotherapy
D Portevin, M Poupot, O Rolland, CO Turrin, JJ Fournié, JP Majoral, AM Caminade, R Poupot |
Journal of Translational Medicine | 2009 |
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Journal of Translational Medicine | 2009 |
Adding fuel to the fire: methamphetamine enhances HIV infection
R Potula, Y Persidsky |
The American Journal of Pathology | 2008 |
HIV-Induced Changes in T Cell Signaling Pathways
M Schweneker, D Favre, JN Martin, SG Deeks, JM McCune |
Journal of immunology (Baltimore, Md. : 1950) | 2008 |
Exploitation of Host Signaling Pathways by B Cell Superantigens--Potential Strategies for Developing Targeted Therapies in Systemic Autoimmunity
M Zouali |
Annals of the New York Academy of Sciences | 2007 |
Studies of HIV-associated immune responses in lymphoid compartments
S Grundström, J Andersson |
Current HIV/AIDS Reports | 2006 |
Regulation of lck degradation and refractory state in CD8+ cytotoxic T lymphocytes
M Uhlin, MG Masucci, V Levitsky |
Proceedings of the National Academy of Sciences | 2005 |
IL-12 reverses anergy to T cell receptor triggering in human lung tumor-associated memory T cells
L Broderick, SP Brooks, H Takita, AN Baer, JM Bernstein, RB Bankert |
Clinical Immunology | 2005 |
Defective CD3γ gene transcription is associated with NFATc2 overexpression in the lymphocytic variant of hypereosinophilic syndrome
KE Willard-Gallo, BM Badran, M Ravoet, A Zerghe, A Burny, P Martiat, M Goldman, F Roufosse, C Sibille |
Experimental Hematology | 2005 |
Increased expression of the natural killer cell inhibitory receptor CD85j/ILT2 on antigen-specific effector CD8 T cells and its impact on CD8 T-cell function
MN Ince, B Harnisch, Z Xu, SK Lee, C Lange, L Moretta, M Lederman, J Lieberman |
Immunology | 2004 |
TCR ζ-chain downregulation: curtailing an excessive inflammatory immune response
M Baniyash |
Nature Reviews Immunology | 2004 |
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AA Ansari |
Autoimmunity Reviews | 2004 |
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JM Clark, AE Annenkov, M Panesar, P Isomäki, Y Chernajovsky, AP Cope |
Proceedings of the National Academy of Sciences | 2004 |
l-Arginine modulates CD3ζ expression and T cell function in activated human T lymphocytes
AH Zea, PC Rodriguez, KS Culotta, CP Hernandez, J DeSalvo, JB Ochoa, HJ Park, J Zabaleta, AC Ochoa |
Cellular Immunology | 2004 |
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JH Finke, RM Bukowski |
2004 | |
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LI Sakkas, G Koussidis, E Avgerinos, J Gaughan, CD Platsoucas |
Clinical and vaccine immunology : CVI | 2004 |
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P Bostik, GL Dodd, F Villinger, AE Mayne, AA Ansari |
Journal of virology | 2004 |
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Whiteside TL |
Cancer Immunology, Immunotherapy | 2004 |
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Antioxidant agents are effective in inducing lymphocyte progression through cell cycle in advanced cancer patients: assessment of the most important laboratory indexes of cachexia and oxidative stress
G Mantovani, A Macci, C Madeddu, L Mura, G Gramignano, MR Lusso, E Massa, M Mocci, R Serpe |
Journal of Molecular Medicine | 2003 |
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S Yousefi, XZ Ma, R Singla, YC Zhou, D Sakac, M Bali, Y Liu, BM Sahai, DR Branch |
Clinical & Experimental Immunology | 2003 |
Effector CD8+CD45RO-CD27-T cells have signalling defects in patients with squamous cell carcinoma of the head and neck
I Kuss, AD Donnenberg, W Gooding, TL Whiteside |
British Journal of Cancer | 2003 |
Effector CD8+CD45RO−CD27−T cells have signalling defects in patients with squamous cell carcinoma of the head and neck
I Kuss, AD Donnenberg, W Gooding, TL Whiteside |
British Journal of Cancer | 2003 |
HIV-1 gp120 induces anergy in naive T lymphocytes through CD4-independent protein kinase-A-mediated signaling
AM Masci, M Galgani, S Cassano, SD Simone, A Gallo, VD Rosa, S Zappacosta, L Racioppi |
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S Krishnan, DL Farber, GC Tsokos |
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D Zhang, P Shankar, Z Xu, B Harnisch, G Chen, C Lange, SJ Lee, H Valdez, MM Lederman, J Lieberman |
Blood | 2003 |
Avoiding the kiss of death: how HIV and other chronic viruses survive
J Lieberman, N Manjunath, P Shankar |
Current Opinion in Immunology | 2002 |
Reactive Oxygen Species Differentially Affect T Cell Receptor-signaling Pathways *
S Cemerski, A Cantagrel, JP van Meerwijk, P Romagnoli |
The Journal of biological chemistry | 2002 |
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BM Badran, SM Wolinsky, A Burny, KE Willard-Gallo |
The Journal of biological chemistry | 2002 |
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ME Keir, MG Rosenberg, JK Sandberg, KA Jordan, A Wiznia, DF Nixon, CA Stoddart, JM McCune |
Journal of immunology (Baltimore, Md. : 1950) | 2002 |
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K Kedzierska, P Ellery, J Mak, SR Lewin, SM Crowe, A Jaworowski |
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J Lieberman, P Shankar, N Manjunath, J Andersson |
Blood | 2001 |
Down-modulation of TCR/CD3 surface complexes after HIV-1 infection is associated with differential expression of the viral regulatory genes
KE Willard-Gallo, M Furtado, A Burny, SM Wolinsky |
European Journal of Immunology | 2001 |
Inhibitors of p56lck: assessing their potential as tools for manipulating T-lymphocyte activation
J Dowden, SG Ward |
Expert Opinion on Therapeutic Patents | 2001 |
Differential Regulation of T Cell Receptor-Mediated Th1 Cell IFN-γProduction and Proliferation by Divergent cAMP-Mediated Redox Pathways
R Cochrane, RB Clark, CK Huang, RE Cone |
Journal of Interferon & Cytokine Research | 2001 |
CD8 T cells specific for human immunodeficiency virus, Epstein-Barr virus, and cytomegalovirus lack molecules for homing to lymphoid sites of infection
G Chen, P Shankar, C Lange, H Valdez, PR Skolnik, L Wu, N Manjunath, J Lieberman |
Blood | 2001 |
A potential role for protein tyrosine kinase p56lck in rheumatoid arthritis synovial fluid T lymphocyte hyporesponsiveness
P Romagnoli, D Strahan, M Pelosi, A Cantagrel, JP van Meerwijk |
International Immunology | 2001 |
Generation and biochemical analysis of human effector CD4 T cells: alterations in tyrosine phosphorylation and loss of CD3ζ expression
S Krishnan, VG Warke, MP Nambiar, HK Wong, GC Tsokos, DL Farber |
Blood | 2001 |
Identification of Protein Kinases Dysregulated in CD4 + T Cells in Pathogenic versus Apathogenic Simian Immunodeficiency Virus Infection
P Bostik, P Wu, GL Dodd, F Villinger, AE Mayne, V Bostik, BD Grimm, D Robinson, HJ Kung, AA Ansari |
Journal of virology | 2001 |
Prolonged Exposure of T Cells to TNF Down-Regulates TCRζ and Expression of the TCR/CD3 Complex at the Cell Surface
P Isomäki, M Panesar, A Annenkov, JM Clark, BM Foxwell, Y Chernajovsky, AP Cope |
Journal of immunology (Baltimore, Md. : 1950) | 2001 |
Immune cell signaling in lupus
GC Tsokos, HK Wong, EJ Enyedy, MP Nambiar |
Current Opinion in Rheumatology | 2000 |
Impaired expression of the CD3-zeta chain in peripheral blood T cells of patients with chronic myeloid leukaemia results in an increased susceptibility to apoptosis
X Chen, A Woiciechowsky, S Raffegerst, D Schendel, HJ Kolb, M Roskrow |
British Journal of Haematology | 2000 |
HIV Type 1-Induced Inhibition of CD45 Tyrosine Phosphatase Activity Correlates with Disease Progression and Apoptosis, but Not with Anti-CD3-Induced T Cell Proliferation
A Giovannetti, M Pierdominici, F Mazzetta, AM Mazzone, G Ricci, A Prozzo, F Pandolfi, R Paganelli, F Aiuti |
AIDS Research and Human Retroviruses | 2000 |
Apoptosis and Its Modulation by Drugs
RG Cameron, G Feuer |
2000 | |
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PA Baars, LM do Couto, JH Leusen, B Hooibrink, TW Kuijpers, SM Lens, RA van Lier |
Journal of immunology (Baltimore, Md. : 1950) | 2000 |
CD3ζ and CD28 down-modulation on CD8 T cells during viral infection
LA Trimble, LW Kam, RS Friedman, Z Xu, J Lieberman |
Blood | 2000 |
Human Immunodeficiency Virus-Specific Circulating CD8 T Lymphocytes Have Down-Modulated CD3ζ and CD28, Key Signaling Molecules for T-Cell Activation
LA Trimble, P Shankar, M Patterson, JP Daily, J Lieberman |
Journal of virology | 2000 |
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SI Gringhuis, A Leow, EA der Voort, PH Remans, FC Breedveld, CL Verweij |
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Impaired function of circulating HIV-specific CD8+ T cells in chronic human immunodeficiency virus infection
P Shankar, M Russo, B Harnisch, M Patterson, P Skolnik, J Lieberman |
Blood | 2000 |
A lack of evidence for down-modulation of CD3 zeta expression in colorectal carcinoma and pregnancy using multiple detection methods
AM Deakin, K Singh, JS Crowe, JH Ellis, A Dalgleish, RJ Leicester, CJ Finlayson, WF Miles, PF Life |
Clinical & Experimental Immunology | 1999 |
Inhibition of p56lckTyrosine Kinase by Isothiazolones
JM Trevillyan, XG Chiou, SJ Ballaron, QM Tang, A Buko, MP Sheets, ML Smith, CB Putman, P Wiedeman, N Tu, D Madar, HT Smith, EJ Gubbins, UP Warrior, YW Chen, KW Mollison, CR Faltynek, SW Djurić |
Archives of Biochemistry and Biophysics | 1999 |
Expression of the T Cell Antigen Receptor ζ Chain following Activation Is Controlled at Distinct Checkpoints: IMPLICATIONS FOR CELL SURFACE RECEPTOR DOWN-MODULATION AND RE-EXPRESSION
N Bronstein-Sitton, L Wang, L Cohen, M Baniyash |
The Journal of biological chemistry | 1999 |
Human Immunodeficiency Virus Type 2 Produces a Defect in CD3-γ Gene Transcripts Similar to That Observed for Human Immunodeficiency Virus Type 1
I Segura, C Delmelle-Wibaut, M Janssens, Y Cleuter, A van den Broeke, R Kettmann, KE Willard-Gallo |
Journal of virology | 1999 |
Apoptosis in asymptomatic HIV-1 seropositives immunized with HIV-1 env glycoprotein (gp160): Effects of administration of Zidovudine in vivo and interleukin-2 in vitro
M Pierdominici, B Mollicone, G Ricci, A Oliva, G D'Offizi, A Giovannetti, F Aiuti, F Pandolfi |
Vaccine | 1998 |
Negative regulation of T cell activation
T Saito |
Current Opinion in Immunology | 1998 |
Down-modulation of the ZAP-70 protein tyrosine kinase in macaque T lymphocytes infected with SIVsmmPBj14
TH Thai, PN Fultz |
Journal of Medical Primatology | 1998 |
Circulating CD8 T Lymphocytes in Human Immunodeficiency Virus-Infected Individuals Have Impaired Function and Downmodulate CD3ζ, the Signaling Chain of the T-Cell Receptor Complex
LA Trimble, J Lieberman |
Blood | 1998 |