gp160 of HIV or anti-CD4 monoclonal antibody ligation of CD4 induces inhibition of JNK and ERK-2 activities in human peripheral CD4+ T lymphocytes.
Eur J Immunol
; 27(2): 397-404, 1997 Feb.
Article
in En
| MEDLINE
| ID: mdl-9045910
ABSTRACT
Under physiological conditions, activation of CD4+ T cells by major histocompatibility complex (MHC)antigen complexes requires engagement of both the T cell receptor and the CD4 molecule. However, CD4 ligands binding to the CD4 molecule has also been shown to inhibit T cell proliferation and interleukin (IL)-2 production in human CD4+ T cells, in an MHC-independent way. We have previously shown that this inhibition was associated with a diminished binding activity of the IL-2 transcription factors NF-AT, NF-kappaB, and AP-1. AP-1 plays a key role in the regulation of IL-2 transcription, and ERK and JNK activities are necessary for regulating AP-1 at both the transcriptional and the post-transcriptional levels. We therefore studied, in human peripheral CD4+ T cells, the regulation of the activities of extracellular signal-regulated protein kinases (ERK) and c-Jun N-terminal kinases (JNK) by two CD4 ligands, gp160 the envelope glycoprotein of human immunodeficiency virus (HIV) and an anti-CD4 monoclonal antibody (mAb). Pre-incubation of CD4+ T lymphocytes in the presence of anti-CD4 mAb or gp160 inhibits the activation of JNK in response to phorbol 12-myristate 13-acetate and ionomycin. In the same conditions, phosphorylation and activation of ERK-2 were also inhibited. Inhibition of both JNK and ERK-2 activities are specific for binding of CD4 ligands to the CD4 molecule. They were not observed in CD8+ T lymphocytes. These results suggest that a specific inhibition of JNK and ERK-2 activities contributes to defective IL-2 production in T lymphocytes pre-incubated with CD4 ligands.
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Database:
MEDLINE
Main subject:
Protein Kinases
/
Protein-Tyrosine Kinases
/
CD4-Positive T-Lymphocytes
/
CD4 Antigens
/
Calcium-Calmodulin-Dependent Protein Kinases
/
HIV Envelope Protein gp160
/
Mitogen-Activated Protein Kinase Kinases
/
JNK Mitogen-Activated Protein Kinases
/
Antibodies, Monoclonal
Limits:
Humans
Language:
En
Year:
1997
Type:
Article