T cell rescue of monocytes from apoptosis: role of the CD40-CD40L interaction and requirement for CD40-mediated induction of protein tyrosine kinase activity.
Circulating monocytes have a limited life span and will undergo apoptosis in the absence of specific stimuli. Recent studies have demonstrated that monocytes can be rescued from apoptosis via lipopolysaccharide (LPS) activation or stimulation with interleukin-1 or tumor necrosis factor-alpha. Based on previous studies from our laboratory, we hypothesized that, in nonseptic (e.g., autoimmune) inflammation, the presence of activated T cells may enhance monocyte longevity through T cell contact-dependent signaling. Plasma membranes prepared from 6 h activated (TmA) and resting (TmR) purified CD4+ T cells were added to resting elutriation-purified monocytes cultured in serum-free medium. Cells were assayed for degree of apoptosis occurring over a 72-h incubation using both agarose gel electrophoresis and flow cytometry. The addition of TmA (but not TmR) was capable of blocking monocyte apoptosis and the ability of TmA to rescue monocytes was abrogated by the addition of anti-CD40L antibodies. Rescue of monocytes from apoptosis could also be mediated by direct cross-linking of monocyte CD40. Inhibitors of tyrosine kinase activity blocked both TmA and anti-CD40-mediated rescue of monocytes from apoptosis, suggesting a primary role of a tyrosine kinase signaling pathway in the events controlling monocyte longevity.
Suttles
J
J
Department of Biochemistry, James H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614, USA.
Evans
M
M
Miller
R W
RW
Poe
J C
JC
Stout
R D
RD
Wahl
L M
LM
D017209:Apoptosis / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000502:physiology*; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand; D002462:Cell Membrane / Q000737:chemistry*; D002469:Cell Separation; D016895:Culture Media, Serum-Free; D004789:Enzyme Activation; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology*; D009000:Monocytes / Q000166:cytology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D019013:CD40 Antigens; D016895:Culture Media, Serum-Free; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D011505:Protein-Tyrosine Kinases