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CD40 ligand is not essential for induction of type 1 cytokine responses or protective immunity after primary or secondary infection with histoplasma capsulatum.

Abstract
The induction of type 1 immune responses (interleukin [IL]-12, interferon [IFN]-gamma) 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-gamma, IL-12, nitric oxide, or tumor necrosis factor alpha. Moreover, CD40L-/- mice treated with anti-IFN-gamma or anti-IL-12 at the time of infection had accelerated mortality, providing further evidence that IL-12 and IFN-gamma 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-gamma had accelerated mortality, demonstrating that IFN-gamma 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.
AuthorsP Zhou, R A Seder
JournalThe Journal of experimental medicine (J Exp Med) Vol. 187 Issue 8 Pg. 1315-24 (Apr 20 1998) ISSN: 0022-1007 [Print] United States
PMID9547342 (Publication Type: Journal Article)
Chemical References
  • Cytokines
  • Membrane Glycoproteins
  • CD40 Ligand
  • Interleukin-12
  • Interferon-gamma
Topics
  • Animals
  • CD40 Ligand
  • Cytokines (biosynthesis)
  • Histoplasmosis (immunology, mortality, prevention & control)
  • Interferon-gamma (immunology)
  • Interleukin-12 (immunology)
  • Leishmaniasis, Cutaneous (immunology)
  • Membrane Glycoproteins (deficiency)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Th1 Cells (immunology)

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