Skip to main content
Article thumbnail
Location of Repository

CD40 Ligand Is Not Essential for Induction of Type 1 Cytokine Responses or Protective Immunity after Primary or Secondary Infection With Histoplasma capsulatum

By Ping Zhou and Robert A. Seder

Abstract

The induction of type 1 immune responses (interleukin [IL]-12, interferon [IFN]-γ) has been shown to be important in mediating protection against many intracellular infections including Histoplasma capsulatum. Costimulatory molecules such as CD40 ligand (CD40L) have been shown to be a central regulator of type 1 responses in vivo. To study the role of CD40L in mediating protection against infection with H. capsulatum, CD40L-deficient (CD40L−/−) and CD40L+/+ mice were infected with H. capsulatum and assessed for various parameters. After a lethal challenge of H. capsulatum, CD40L−/− mice were not substantially different from CD40L+/+ mice in terms of mortality, fungal burden, or production of IFN-γ, IL-12, nitric oxide, or tumor necrosis factor α. Moreover, CD40L−/− mice treated with anti–IFN-γ or anti–IL-12 at the time of infection had accelerated mortality, providing further evidence that IL-12 and IFN-γ are produced in vivo in the absence of CD40L. In addition, CD40L−/− mice infected with a sublethal dose of H. capsulatum survived infection, whereas all mice infected with the same dose and treated with anti–IFN-γ had accelerated mortality, demonstrating that IFN-γ but not CD40L was essential for primary immunity to H. capsulatum infection. Interestingly, depletion of either CD4+ or CD8+ T cells resulted in accelerated mortality in CD40L−/− mice, suggesting a critical role for these cells in response to infection. Finally, CD40L−/− mice initially infected with a sublethal dose of H. capsulatum were protected from secondary infection with a lethal dose of H. capsulatum, demonstrating that CD40L is not required for the maintenance of memory immunity

Topics: Article
Publisher: The Rockefeller University Press
OAI identifier: oai:pubmedcentral.nih.gov:2212226
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    Citations

    1. (1996). A role for CD41NK1.11 T lymphocytes as major histocompatibility complex class II independent helper cells in the generation of CD81 effector function against intracellular infection.
    2. (1993). Activated T cells induce expression of B7/BB1 on normal or leukemic B cells through a CD40-dependent signal.
    3. (1995). Activated T cells induced interleukin-12 production by monocytes via CD40–CD40 ligand interaction.
    4. (1995). Antibodies to interleukin 12 abrogate established experimental colitis in mice.
    5. (1997). Antigen-driven but not lipopolysaccharide-driven IL-12 production in macrophages requires triggering of CD40.
    6. (1996). Blocking the CD40L–CD40 interaction in vivo specifically prevents the priming of T helper 1 cells through the inhibition of interleukin 12 secretion.
    7. (1996). CD40 and its ligand in host defense.
    8. (1996). CD40 ligand is required for protective cell-mediated immunity to Leishmania major.
    9. (1996). CD40 ligand–deficient mice generate a normal primary cytotoxic T-lymphocyte response but a defective humoral response to a viral infection.
    10. (1996). CD40 ligand–dependent T cell activation: requirement of B7-CD28 signaling through CD40.
    11. (1998). CD40 ligand/CD40 stimulation regulates the production of IFN-g from human PBMCs in an IL-12– and/ or CD28–dependent manner.
    12. (1996). CD40-CD40 ligand interactions in experimental allergic encephalomyelitis and multiple sclerosis.
    13. (1996). CD40–CD40 ligand interactions are critical in T–B cooperation but not for other anti-viral CD41 T cell functions.
    14. (1996). CD40/CD40 ligand interactions are required for T cell–dependent production of IL-12 by mouse macrophages.
    15. (1996). CD40L is important for induction of, but not response to, costimulatory activity: ICAM-1 as the second costimulatory molecule rapidly up-regulated by CD40L.
    16. (1996). CD40L-deficient mice show deficits in antiviral immunity and have an impaired memory CD81 CTL response.
    17. (1994). CD81 T cell–mediated protection against an intracellular bacterium by perforin-dependent cytotoxicity.
    18. (1983). Characterization of the murine T cell surface molecule, designated L3T4 identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule.
    19. (1994). Class II major histocompatibility complex–deficient mice initially control an infection with Leishmania major but succumb to the disease.
    20. Disruption of CD40-CD40 ligand interactions results in an enhanced susceptibility to Leishmania amazonensis infection.
    21. (1990). Disseminated histoplasmosis in the acquired immune deficiency syndrome: clinical finding, diagnosis and treatment, and review of the literature. Medicine
    22. (1998). Factors involved in regulating primary and secondary immunity to infection with Histoplasma capsulatum: TNF-a plays a critical role in maintaining secondary immunity in the absence of IFN-g.
    23. (1993). Helper T-cells without CD4: control of leishmaniasis in CD4-deficient mice.
    24. (1996). High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10.
    25. (1994). Humoral immune responses in CD40 ligand– deficient mice.
    26. (1980). IgG and IgM monoclonal antibodies reactive with different determinants of the molecular complex bearing Lyt2 antigen block T cell–mediated cytolysis in the absence of complement.
    27. (1995). IL-12 prevents mortality in mice infected with Histoplasma capsulatum through induction of IFN-g.
    28. (1995). Immune response to Mycobacterium bovis bacille Calmette Guerin infection in major histocompatibility complex class I– and II– deficient knock-out mice: contribution of CD4 and CD8 T cells to acquired resistance.
    29. (1995). Impairment of antigen-specific T cell priming in mice lacking CD40 ligand.
    30. (1997). Induction of a CD81 cytotoxic T lymphocyte response by cross-priming requires cognate CD41 T cell help.
    31. (1993). Interleukin-12 is required for the T-lymphocyte– independent induction of interferon g by an intracellular parasite and induces resistance in T-cell–deficient hosts.
    32. (1987). Involvement of specific Lyt-21 T cells in the immunological control of experimentally induced murine cutaneous Leishmania.
    33. (1994). Leishmania promastigotes evade interleukin1324 CD40 Ligand Is Not Required for Th1 Responses In Vivo to Infection 12 (IL-12) induction by macrophages and stimulate a broad range of cytokines from CD401 T cells during initiation of infection.
    34. (1996). Leishmania promastigotes selectively inhibit interleukin 12 induction in bone marrow-derived macrophages from susceptible and resistant mice.
    35. (1996). Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T–T help via APC activation.
    36. (1992). Major histocompatibility complex class I–restricted T cells are required for resistance to Mycobacterium tuberculosis infection.
    37. (1997). Modulation of immune responses in murine pulmonary histoplasmosis.
    38. (1994). Neutralization of IL-12 decreases resistance to Listeria in SCID and C.B-17 mice. Reversal by IFN-g.
    39. (1997). Perforin-mediated cytolysis plays a limited role in host resistance to Toxoplasma gondii.
    40. (1997). Perforin, a cytotoxic molecule which mediates cell necrosis, is not required for the early control of mycobacterial infection in mice.
    41. (1995). Prevention of experimental autoimmune encephalomyelitis by antibodies against interleukin 12.
    42. (1988). Progressive disseminated histoplasmosis in patients with acquired immunodeficiency syndrome.
    43. Progressive loss of CD81 T cell–mediated control of a g-herpesvirus in the absence of CD41 T cells.
    44. (1996). Protective role of CD40 in Leishmania major infection at two distinct phases of cell-mediated immunity.
    45. (1995). Rapid induction of a novel costimulatory activity on B cells to CD40 ligand.
    46. (1995). Regulation of interleukin-12 expression in human monocytes: selective priming by interferon-g of lipopolysaccharide-inducible p35 and p40 genes.
    47. (1996). Requirement for CD40 ligand in costimulation induction, T cell activation, and experimental allergic encephalomyelitis.
    48. (1994). Role of CD81 T cells in host resistance to systemic infection with Histoplasma capsulatum in mice.
    49. (1995). Specific immunity to Listeria monocytogenes in the absence of IFN-g.
    50. (1995). Stimulation of CD40 with purified soluble gp39 induces proinflammatory re-1323 Zhou et al. sponses in human monocytes.
    51. (1995). Studies on the interdependence of gp39 and B7 expression and function during antigen-specific immune responses.
    52. The course of Mycobacterium tuberculosis infection in the lungs of mice lacking expression of either perforin- or granzyme-mediated cytolytic mechanisms.
    53. (1996). The interleukin 12 p40 gene promoter is primed by interferon g in monocytic cells.
    54. (1996). The role of CD40 ligand in costimulation to T-cell activation.
    55. (1987). Two types of mouse helper T cell clone.
    56. (1997). Vaccination with DNA encoding the immunodominant LACK parasite antigen confers protective immunity to mice infected with Leishmania major.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.