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Infection and Immunity, July 2002, p. 3759-3767, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3759-3767.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Cellular and Molecular Regulation of Vaccination with Heat Shock Protein 60 from Histoplasma capsulatum

George S. Deepe Jr.,,1,,2* and Reta S. Gibbons2

Veterans Affairs Hospital,2 Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio1

Received 12 February 2002/ Returned for modification 22 March 2002/ Accepted 16 April 2002

Vaccination with heat shock protein 60 (Hsp60) from Histoplasma capsulatum induces a protective immune response in mice. We explored the cellular and molecular requirements for the efficacy of recombinant Hsp60 in mice. Depletion of CD4+, but not CD8+, cells during the inductive phase of vaccination abolished protection, as assessed by survival and by the fungal burden in lungs and spleens. In the expressive phase, the elimination of CD4+ or CD8+ cells after immunization did not significantly alter fungal recovery or survival from a lethal challenge. Depletion of both subpopulations after Hsp60 vaccination resulted in a failure to control a lethal infection and a higher fungal burden in lungs and spleens. Cytokine release by spleen cells from mice vaccinated with Hsp60 produced substantially more gamma interferon and interleukin-10 and -12 than that of cells from mice immunized with either H. capsulatum recombinant Hsp70 or bovine serum albumin. The generation of gamma interferon, but not of interleukin-10, was dependent on T cells, in particular CD4+ cells. Treatment of Hsp60-immunized mice with monoclonal antibody to gamma interferon or interleukin-10 or -12 in the inductive phase of vaccination was accompanied by increased recovery of yeast cells from lungs and spleens and 100% mortality. Likewise, the neutralization of gamma interferon or interleukin-12 abolished the protective effect of Hsp60 in the expressive phase. These results delineate the complexity of the regulatory elements necessary for vaccination against this fungus.


* Corresponding author. Mailing address: Division of Infectious Diseases, Dept. of Medicine, 231 Albert Sabin Way, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0560. Phone: (513) 558-4704. Fax: (513) 558-2089. E-mail: george.deepe{at}uc.edu.

Editor: T. R. Kozel


Infection and Immunity, July 2002, p. 3759-3767, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3759-3767.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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