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J. Exp. Med.,
Volume 187, Number 8, April 20, 1998 1315-1324
By
From the Clinical Immunology Section, Laboratory of Clinical Investigation, National Institute of
Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
The induction of type 1 immune responses (interleukin [IL]-12, interferon [IFN]-
) 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-, IL-12, nitric
oxide, or tumor necrosis factor 
. Moreover, CD40L/ mice treated with anti-IFN- or
anti-IL-12 at the time of infection had accelerated mortality, providing further evidence that
IL-12 and IFN- 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- had accelerated mortality, demonstrating that IFN- 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.
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