The effects of CD3, CD4 and CD28 signaling on lymphocytes during human immunodeficiency virus-1 infection
| Autor: | Richard Qihao Zheng, Keith E. Nye, Christine Guntermann |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
MAPK/ERK pathway
CD3 Complex Cell Survival CD3 Immunology Receptors Antigen T-Cell chemical and pharmacologic phenomena Apoptosis HIV Infections Biology In Vitro Techniques chemistry.chemical_compound CD28 Antigens Immunology and Allergy Humans Lymphocytes Phosphorylation Protein kinase A Serine/threonine-specific protein kinase ZAP-70 Protein-Tyrosine Kinase T-cell receptor JAK-STAT signaling pathway hemic and immune systems Tyrosine phosphorylation Protein-Tyrosine Kinases chemistry CD4 Antigens Calcium-Calmodulin-Dependent Protein Kinases biology.protein Cancer research HIV-1 Tyrosine Tyrosine kinase Signal Transduction |
| Zdroj: | European journal of immunology. 27(8) |
| ISSN: | 0014-2980 |
| Popis: | We investigated the effects of early human immunodeficiency virus-1 infection (HIV-1) on CD4- and CD28-mediated co-signaling of the T cell receptor (TCR)/CD3 complex in peripheral blood lymphocytes (PBL). CD4 ligation either alone or in conjunction with TCR occupancy resulted in abrogated signaling shown by impaired co-association of the tyrosine kinase ZAP-70 with the CD3-zeta chains in virally infected PBL. In addition, down-regulation of CD4-associated TCR signaling resulted in diminished tyrosine phosphorylation of mitogen-activated protein kinase (MAPK), a serine threonine kinase which is critically involved in the regulation of transcription factors. Furthermore, these aberrant CD4-driven signals rendered HIV-1-infected PBL susceptible to activation-induced cell death. By contrast, cross-linking of the TCR/CD3 complex with the CD28 receptor improved tyrosine phosphorylation of MAPK and salvaged infected PBL from activation-induced cell death. Our data demonstrate the importance of appropriate CD3, CD4 and CD28 co-stimulatory function to prevent apoptosis. The CD4-mediated signaling defects of the TCR could contribute to the loss of immunocompetent cells during HIV-1 infection via activation-induced cell death, whereas stimulation through the CD28 pathway could reverse these detrimental effects. |
| Databáze: | OpenAIRE |
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