Cellular and molecular regulation of vaccination with heat shock protein 60 from Histoplasma capsulatum.
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.
Deepe
George S
GS
Veterans Affairs Hospital and Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0560, USA. george.deepe@uc.edu
Gibbons
Reta S
RS
D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018834:Chaperonin 60 / Q000276:immunology*; D004195:Disease Models, Animal; D005657:Fungal Vaccines / Q000276:immunology*; D006658:Histoplasma / Q000276:immunology; D006660:Histoplasmosis / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
D000946:Antigens, Fungal; D018834:Chaperonin 60; D005657:Fungal Vaccines; D014409:Tumor Necrosis Factor-alpha; D014614:Vaccines, Synthetic; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma