Depletion of Dendritic Cells, But Not Macrophages, in Patients with Sepsis

Dendritic cells (DCs) are a group of APCs that have an extraordinary capacity to interact with T and B cells and modulate their responses to invading pathogens. Although a number of defects in the immune system have been identified in sepsis, few studies have examined the effect of sepsis on DCs, which is the purpose of this study. In addition, this study investigated the effect of sepsis on macrophages, which are reported to undergo apoptosis, and MHC II expression, which has been noted to be decreased in sepsis. Spleens from 26 septic patients and 20 trauma patients were evaluated by immunohistochemical staining. Although sepsis did not decrease the number of macrophages, sepsis did cause a dramatic reduction in the percentage area of spleen occupied by FDCs, i.e., 2.9 ± 0.4 vs 0.7 ± 0.2% in trauma and septic patients, respectively. The number of MHC II-expressing cells, including interdigitating DCs, was decreased in septic, compared with trauma, patients. However, sepsis did not appear to induce a loss of MHC II expression in those B cells, macrophages, or DCs that were still present. The dramatic loss of DCs in sepsis may significantly impair B and T cell function and contribute to the immune suppression that is a hallmark of the disorder.

[1]  J. D. de Fijter,et al.  Rapamycin induces apoptosis in monocyte- and CD34-derived dendritic cells but not in monocytes and macrophages. , 2001, Blood.

[2]  G. Clermont,et al.  Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care , 2001, Critical care medicine.

[3]  M. Levin,et al.  Bactericidal/permeability-increasing protein—Lessons learned from the phase III, randomized, clinical trial of rBPI21 for adjunctive treatment of children with severe meningococcemia , 2001, Critical care medicine.

[4]  R. Hotchkiss,et al.  Sepsis-Induced Apoptosis Causes Progressive Profound Depletion of B and CD4+ T Lymphocytes in Humans1 , 2001, The Journal of Immunology.

[5]  L. Moldawer,et al.  Apoptosis in sepsis: a new target for therapeutic exploration , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[6]  O. Eremin,et al.  Dendritic cells (I): Biological functions. , 2001, Journal of the Royal College of Surgeons of Edinburgh.

[7]  F. Sallusto,et al.  Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells , 2000, Nature Immunology.

[8]  A. Sher,et al.  The role of dendritic cells in the induction and regulation of immunity to microbial infection. , 1999, Current opinion in immunology.

[9]  R. Hotchkiss,et al.  Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. , 1999, Critical care medicine.

[10]  S. Korsmeyer,et al.  Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis. , 1999, Journal of immunology.

[11]  J. Lederer,et al.  The effects of injury on the adaptive immune response. , 1999, Shock.

[12]  Y. Abu Kwaik,et al.  Apoptosis in Macrophages and Alveolar Epithelial Cells during Early Stages of Infection by Legionella pneumophila and Its Role in Cytopathogenicity , 1999, Infection and Immunity.

[13]  M. Moser,et al.  Antigen-specific T lymphocytes regulate lipopolysaccharide-induced apoptosis of dendritic cells in vivo. , 1998, Journal of immunology.

[14]  J. Puyana,et al.  Both T-helper-1- and T-helper-2-type lymphokines are depressed in posttrauma anergy. , 1998, The Journal of trauma.

[15]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[16]  I. Chaudry,et al.  Prolonged immunodepression after trauma and hemorrhagic shock. , 1998, The Journal of trauma.

[17]  T. Brocker Survival of Mature CD4 T Lymphocytes Is Dependent on Major Histocompatibility Complex Class II–expressing Dendritic Cells , 1997, The Journal of experimental medicine.

[18]  K. Asadullah,et al.  Monocyte deactivation in septic patients: Restoration by IFN-γ treatment , 1997, Nature Medicine.

[19]  I. Chaudry,et al.  Differential induction of apoptosis in lymphoid tissues during sepsis: variation in onset, frequency, and the nature of the mediators. , 1996, Blood.

[20]  I. Chaudry,et al.  THE INDUCTION OF ACCELERATED THYMIC PROGRAMMED CELL DEATH DURING POLYMICROBIAL SEPSIS: CONTROL BY CORTICOSTEROIDS BUT NOT TUMOR NECROSIS FACTOR , 1995, Shock.

[21]  C. Meijer,et al.  A new monoclonal antibody (3A5) that recognises a fixative resistant epitope on tissue macrophages and monocytes. , 1994, Journal of clinical pathology.

[22]  C. Dijkstra,et al.  The functional state of follicular dendritic cells in severe combined immunodeficient (SCID) mice: Role of the lymphocytes , 1994, European journal of immunology.

[23]  J. Meakins,et al.  Delayed Hypersensitivity: Indicator of Acquired Failure of Host Defenses in Sepsis and Trauma , 1977, Annals of surgery.

[24]  I. Hermans,et al.  Killing of Dendritic Cells: A Life Cut Short or a Purposeful Death? , 2001 .