Abstract
The present study investigates the role of the HIV-suppressive beta-chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1 and RANTES in activation-induced cell death (AICD). A pool of these beta-chemokines reduced anti-CD3-induced apoptosis of T cell blasts from healthy blood donors in a dose-dependent manner. Although the pooled beta-chemokines were more effective, the inhibitory effect could also be mediated by each of the individual chemokines and was blocked by neutralizing anti-chemokine antibodies. The beta-chemokines also inhibited pokeweed mitogen/staphylococcal enterotoxin B-induced T lymphocyte apoptosis in 33/49 HIV-infected (HIV+) individuals. This anti-apoptotic effect was not correlated with the patients' CD4 T cell counts. beta-chemokines did not lead to altered secretion of IL-2, IL-4, IFN-gamma or IL-10 in response to activation stimuli in either normal T cell blasts or peripheral blood mononuclear cells from HIV+ individuals. Co-incubation with beta-chemokines did not inhibit anti-CD3-induced expression of cell surface Fas ligand, nor did it alter levels of the death receptor Fas or Bcl-2 in T cell blasts, suggesting that the beta-chemokines are blocking AICD downstream of Fas. These observations indicate that beta-chemokines may play a novel role as modulators of AICD, in addition to their known role as chemoattractants and inhibitors of HIV replication.
MeSH terms
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Antigens, CD / biosynthesis
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Antigens, Differentiation, T-Lymphocyte / biosynthesis
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Apoptosis / drug effects
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Apoptosis / immunology*
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CD3 Complex / immunology
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Cells, Cultured
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Chemokine CCL3
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Chemokine CCL4
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Chemokine CCL5 / biosynthesis
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Chemokine CCL5 / immunology*
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Chemokine CCL5 / pharmacology
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Chemokines, CC / pharmacology
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Enterotoxins / pharmacology
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Fas Ligand Protein
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HIV Infections / blood
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HIV Infections / immunology*
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Humans
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Interferon-gamma / biosynthesis
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Interleukin-10 / biosynthesis
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Interleukin-2 / biosynthesis
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Interleukin-4 / biosynthesis
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Lectins, C-Type
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology*
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Macrophage Inflammatory Proteins / biosynthesis
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Macrophage Inflammatory Proteins / immunology*
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Macrophage Inflammatory Proteins / pharmacology
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Membrane Glycoproteins / biosynthesis
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Pokeweed Mitogens / pharmacology
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Staphylococcus aureus
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T-Lymphocytes / cytology
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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fas Receptor / biosynthesis
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD3 Complex
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CD69 antigen
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Chemokine CCL3
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Chemokine CCL4
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Chemokine CCL5
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Chemokines, CC
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Enterotoxins
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FASLG protein, human
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Fas Ligand Protein
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Interleukin-2
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Lectins, C-Type
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Macrophage Inflammatory Proteins
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Membrane Glycoproteins
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Pokeweed Mitogens
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Proto-Oncogene Proteins c-bcl-2
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fas Receptor
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Interleukin-10
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Interleukin-4
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enterotoxin B, staphylococcal
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Interferon-gamma