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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Freed, J. H. Campbell, P. A. Newell, M. K. Desbarats, J. |
| Description | Author Affiliation: Desbarats J ( Division of Basic Immunology, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.); |
| Abstract | The CD4 receptor contributes to T-cell activation by coligating major histocompatibility complex class II on antigen presenting cells with the T-cell receptor (TCR)/CD3 complex, and triggering a cascade of signaling events including tyrosine phosphorylation of intracellular proteins. Paradoxically, CD3 cross-linking prior to TCR stimulation results in apoptotic cell death, as does injection of anti-CD4 antibodies in vivo of CD4 ligation by HIV glycoprotein (gp) 120. In this report we investigate the mechanism by which CD4 cross-linking induces cell death. We have found that CD4 cross-linking results in a small but rapid increase in levels of cell surface Fas, a member of the tumor necrosis factor receptor family implicated in apoptotic death and maintenance of immune homeostasis. Importantly, CD4 cross-linking triggered the ability of Fas to function as a death molecule. Subsequent to CD4 cross-linking, CD4+ splenocytes cultured overnight became sensitive to Fas-mediated death. Death was Fas-dependent, as demonstrated by cell survival in the absence of plate-bound anti-Fas antibody, and by the lack of CD4-induced death in cells from Fas-defective lymphoproliferative (lpr) mice. We demonstrate here that CD4 regulates the ability of Fas to induce cell death in Cd4+ T cells. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 20 |
| Volume Number | 93 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1996-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antigens, CD4 Physiology Antigens, CD95 Metabolism Apoptosis CD4-Positive T-Lymphocytes Mice, Inbred MRL Lpr Immunology T-Lymphocyte Subsets Cytology Animals Cells, Cultured HIV Infections Mice Mice, Inbred C3H Receptor Aggregation Spleen Th1 Cells Up-Regulation Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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