TY - JOUR
T1 - Downregulation of CD40 ligand response in monocytes from sepsis patients
AU - Sinistro, Anna
AU - Almerighi, Cristiana
AU - Ciaprini, Chiara
AU - Natoli, Silvia
AU - Sussarello, Emanuele
AU - Di Fino, Sara
AU - Calò-Carducci, Francesca
AU - Rocchi, Giovanni
AU - Bergamini, Alberto
PY - 2008/12
Y1 - 2008/12
N2 - It has been suggested that a defective adaptive immune response contributes to septic immunosuppression. Here, the response of monocytes to CD40 ligand (CD40L) for patients with sepsis due to infection with gram-negative organisms has been analyzed. Compared to cells from controls, monocytes from septic patients showed significantly reduced production of tumor necrosis factor alpha, interleukin-1β (IL-1β), and IL-12 and were unable to acquire high levels of CD80 and CD86 molecules. These alterations were observed at the onset of sepsis and persisted at day 7. However, the ability of monocytes to respond to CD40L stimulation was partially but significantly restored in cells from patients who recovered from sepsis. In addition, costimulation of autologous CD4+ T lymphocytes by CD40L-activated monocytes from septic patients failed to induce cell proliferation and gamma interferon production. Finally, the ability of CD40L to rescue monocytes from apoptosis was severely impaired. We conclude that downregulation of the CD40L response may be an appropriate model for the monocyte alteration observed during septic immunosuppression and may help in the development of novel therapeutic strategies.
AB - It has been suggested that a defective adaptive immune response contributes to septic immunosuppression. Here, the response of monocytes to CD40 ligand (CD40L) for patients with sepsis due to infection with gram-negative organisms has been analyzed. Compared to cells from controls, monocytes from septic patients showed significantly reduced production of tumor necrosis factor alpha, interleukin-1β (IL-1β), and IL-12 and were unable to acquire high levels of CD80 and CD86 molecules. These alterations were observed at the onset of sepsis and persisted at day 7. However, the ability of monocytes to respond to CD40L stimulation was partially but significantly restored in cells from patients who recovered from sepsis. In addition, costimulation of autologous CD4+ T lymphocytes by CD40L-activated monocytes from septic patients failed to induce cell proliferation and gamma interferon production. Finally, the ability of CD40L to rescue monocytes from apoptosis was severely impaired. We conclude that downregulation of the CD40L response may be an appropriate model for the monocyte alteration observed during septic immunosuppression and may help in the development of novel therapeutic strategies.
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U2 - 10.1128/CVI.00184-08
DO - 10.1128/CVI.00184-08
M3 - Article
C2 - 18945879
AN - SCOPUS:57349140752
VL - 15
SP - 1851
EP - 1858
JO - Clinical and Vaccine Immunology
JF - Clinical and Vaccine Immunology
SN - 1556-6811
IS - 12
ER -