Beta-chemokines inhibit activation-induced death of lymphocytes from HIV-infected individuals

Eur J Immunol. 2000 Jul;30(7):2048-55. doi: 10.1002/1521-4141(200007)30:7<2048::AID-IMMU2048>3.0.CO;2-I.

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

  • Antigens, CD / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • Apoptosis / drug effects
  • Apoptosis / immunology*
  • CD3 Complex / immunology
  • Cells, Cultured
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5 / biosynthesis
  • Chemokine CCL5 / immunology*
  • Chemokine CCL5 / pharmacology
  • Chemokines, CC / pharmacology
  • Enterotoxins / pharmacology
  • Fas Ligand Protein
  • HIV Infections / blood
  • HIV Infections / immunology*
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / biosynthesis
  • Interleukin-2 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Lectins, C-Type
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology*
  • Macrophage Inflammatory Proteins / biosynthesis
  • Macrophage Inflammatory Proteins / immunology*
  • Macrophage Inflammatory Proteins / pharmacology
  • Membrane Glycoproteins / biosynthesis
  • Pokeweed Mitogens / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Staphylococcus aureus
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • fas Receptor / biosynthesis

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • CD69 antigen
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokines, CC
  • Enterotoxins
  • FASLG protein, human
  • Fas Ligand Protein
  • Interleukin-2
  • Lectins, C-Type
  • Macrophage Inflammatory Proteins
  • Membrane Glycoproteins
  • Pokeweed Mitogens
  • Proto-Oncogene Proteins c-bcl-2
  • fas Receptor
  • Interleukin-10
  • Interleukin-4
  • enterotoxin B, staphylococcal
  • Interferon-gamma