Differential CD4-dependent inhibition of JNK but not Erk-2 activities in human naive and memory CD4+ T cell populations.
CD4 ligand binding to the CD4 molecules has been shown to inhibit T cell proliferation and IL-2 transcription and synthesis. We have recently shown that this inhibition correlated with a CD4-mediated inhibition of the kinase Erk-2 and c-Jun-N-terminal kinases (JNK) which play a key role in IL-2 transcription. Moreover, we have previously reported that antigen-independent adhesion of CD45RObright/CD4+ T cells to B cells is negatively regulated by CD4 ligands, whereas that of CD45RAbright/CD4+ naive T cells is not. Other groups have described, in murine models, a differential sensitivity of memory and naive T cells to CD4-mediated inhibitory effects on T cell activation. The aim of the present report was to study the sensitivity of the naive and memory CD4+ T cell populations to the CD4-mediated inhibition of Erk-2 and JNK activation. Our data show that preincubation with anti-CD4 mAb, of the CD45RAbright/CD4+ naive and the CD45RObright/CD4+ memory human T cell populations, induces inhibition of both Erk-2 phosphorylation and Erk-2 activation by phorbol ester or anti-CD3 mAb. In contrast, CD3 mediated JNK activation was inhibited in the memory but not in the naive CD4+ T cell population, whereas JNK activation by phorbol ester or phorbol esters plus Ca2+ ionophore was inhibited by anti-CD4 mAb in both T cell populations. These data further demonstrate a differential sensitivity of naive and memory CD4+ T cell populations to the CD4-mediated negative signaling.
INSERM U429, Pavillon Kirmisson, Hôpital Necker-Enfants-Malades, Paris, France.
A
A
Pallier
S
S
Jauliac
N
N
Jabado
A
A
Fischer
C
C
Hivroz
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004789:Enzyme Activation; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007476:Ionophores / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D019950:Mitogen-Activated Protein Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D047428:Protein Kinase Inhibitors; D012680:Sensitivity and Specificity; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007476:Ionophores; D047428:Protein Kinase Inhibitors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D013755:Tetradecanoylphorbol Acetate