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Alteration of pulmonary immunity to Listeria monocytogenes by diesel exhaust particles (DEPs). II. Effects of DEPs on T-cell-mediated immune responses in rats.

By Xue-Jun Yin, Rosana Schafer, Jane Y C Ma, James M Antonini, Jenny R Roberts, David N Weissman, Paul D Siegel and Joseph K H Ma


Previously, we showed that diesel exhaust particles (DEPs) suppressed pulmonary clearance of Listeria monocytogenes (Listeria) and inhibited the phagocytosis of alveolar macrophages and their response to Listeria in the secretion of interleukin (IL)-1 beta, tumor necrosis factor alpha, and IL-12. In this report we examined the effects of DEPs and/or Listeria on T-cell development and secretion of IL-2, IL-6, and interferon (IFN)-gamma. We exposed Brown Norway rats to clean air or DEPs at 50 or 100 mg/m3 for 4 hr by nose-only inhalation and inoculated with 100,000 Listeria. Lymphocytes in the lung-draining lymph nodes were isolated at 3 and 7 days postexposure, analyzed for CD4+ and CD8+ cells, and measured for cytokine production in response to concanavalin A or heat-killed L. monocytogenes. Listeria infection induced lymphocyte production of IL-6. At 7 days postinfection, lymphocytes from Listeria-infected rats showed significant increases in CD4+ and CD8+ cell counts and the CD8+/CD4+ ratio and exhibited increased production of IFN-gamma and IL-2 receptor expression compared with the noninfected control. These results suggest an immune response that involves the action of IL-6 on T-cell activation, yielding Listeria-specific CD8+ cells. DEP exposure alone enhanced lymphocyte production of both IL-2 and IL-6 but inhibited lymphocyte secretion of IFN-gamma. In rats exposed to 100 mg/m3 DEPs and Listeria, a 10-fold increase occurred in pulmonary bacterial count at 3 days postinfection when compared with the Listeria-only exposure group. The isolated lymphocytes showed a significant increase in the CD4+ and CD8+ cell counts and the CD8+/CD4+ ratio and exhibited increased IL-2 responsiveness and increased capacity in the secretion of IL-2, IL-6, and IFN-gamma. This T-cell immune response was sufficient to allow the Brown Norway rats to clear the bacteria at 7 days postinfection and overcome the down-regulation of the innate immunity by the acute DEP exposure

Topics: Research Article
Year: 2003
OAI identifier:
Provided by: PubMed Central

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  1. (1989). Accessory signals in murine cytolytic T cell responses: dual requirement for IL1 and IL-6.
  2. (2002). Alteration of pulmonary immunity to Listeria monocytogenes by diesel exhaust particles (DEP). I. Effects of DEP on early pulmonary responses. Environ Health Perspect 110:1105–1111.
  3. (1988). B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes.
  4. (1990). Biological and clinical aspects of interleukin 6. Immunol Today 11:443–449.
  5. (1990). Cytokines in antibacterial resistance: possible applications for immunomodulation. Lung 168(suppl):1025–1032.
  6. (1997). Cytokines in the induction and expression of T cell-mediated granuloma formation and protection in the murine model of listeriosis.
  7. (1981). Deposition and clearance of inhaled diesel exhaust particles in the respiratory tract of Fischer rats.
  8. (1994). Diesel exhaust particles induce local IgE production in vivo and alter the pattern of IgE messenger RNA isoforms.
  9. (2001). Diesel exhaust particles suppress macrophage function and slow the pulmonary clearance of Listeria monocytogenes in rats. Environ Health Perspect 109:515–521.
  10. (1996). Effects of amiodarone-induced phospholipidosis on pulmonary host defense functions in rats.
  11. (1999). Effects of diesel exhaust particles (DEP), carbon black, and silica on macrophage responses to lipopolysaccharide: evidence of DEP suppression of macrophage activity.
  12. (1997). Effects of diesel exhaust particles on the secretion of interleukin-1 and tumor necrosis factor-alpha from rat alveolar macrophages. Exp Lung Res 23:269–284.
  13. (1999). Enhancement of collagen-induced arthritis in mice by diesel exhaust particles.
  14. (1999). IFN-gamma potentiates the release of TNF-alpha and MIP-1alpha by alveolar macrophages during allergic reactions.
  15. (2001). IL-12: keeping cell-mediated immunity alive.
  16. (1993). Immunity to intracellular bacteria. Annu Rev Immnol 11:129–163.
  17. (1991). Induction of cytotoxic T lymphocyte development from murine thymocytes by IL-1 and IL-6.
  18. (1997). Inhalation of diesel exhaust enhances antigen-specific IgE antibody production in mice.
  19. (1995). Interleukin 12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol 13:251–276.
  20. (1998). Interleukin-12: a cytokine at the interface of inflammation and immunity. Adv Immunol 70:83–243.
  21. (2000). Listeria monocytogenes as a shortlived delivery system for the induction of type 1 cell-mediated immunity against the p36/LACK antigen of Leishmania major.
  22. (1995). Listeria monocytogenes: a live vector able to deliver heterologous protein within the cytosol and to drive a CD8 dependent T cell response.
  23. (1997). Listeria monocytogenes: a potent vaccine vector for neoplastic and infectious disease. Immunol Rev 158:159–169.
  24. (1992). Mouse splenic macrophage cell lines with different antigen-presenting activities for CD4+ helper T cell subsets and allogeneic CD8+ T cells. Cell Immunol 145:359–371.
  25. (1997). Murine listeriosis as a model of antimicrobial defense.
  26. (1998). Pulmonary host defenses.
  27. (1998). Quantitative morphometric analysis of pulmonary deposition of aerosol particles inhaled via intratracheal nebulization, intratracheal instillation or nose-only inhalation in rats.
  28. (1994). Regulation of the human interleukin-2/interleukin-2 receptor system: a role for immunosuppression. Proc Soc Exp Biol Med 206:176–180.
  29. (1991). Retention modeling of diesel exhaust particles in rats and humans. Res Rep Health Eff Inst 40:1–24.
  30. (2000). Subchronic silica exposure enhances respiratory defense mechanisms and the pulmonary clearance of Listeria monocytogenes in rats.

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