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Antigen-induced protective and nonprotective cell-mediated immune components against Cryptococcus neoformans
J W Murphy1, F Schafer, A Casadevall
1Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, USA. juneann-murphy@uokhsc.edu
Infection and Immunity
|May 29, 1998
Summary
Mice immunized with a soluble antigen (CneF-CFA) showed better protection against Cryptococcus neoformans than heat-killed cells (HKC). This highlights distinct T-cell responses, with CneF-CFA inducing protective immunity.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Cryptococcus neoformans causes life-threatening fungal infections.
- Understanding T-cell mediated immunity is crucial for developing effective vaccines and therapies.
- Different antigen preparations elicit distinct T-cell responses.
Purpose of the Study:
- To compare the protective immunity induced by two different Cryptococcus neoformans antigen preparations.
- To identify which activated T-cell profile confers better protection against cryptococcal challenge.
- To elucidate the role of specific T-cell subsets in antifungal immunity.
Main Methods:
- Immunization of CBA/J mice with soluble culture filtrate antigen (CneF) in complete Freund's adjuvant (CFA) or heat-killed C. neoformans cells (HKC).
- Assessment of T-cell activation profiles, including CD4+ and CD8+ T cells.
- Evaluation of protective responses through C. neoformans clearance, survival rates, and lesion development after challenge with viable C. neoformans.
- Measurement of delayed-type hypersensitivity (DTH) responses and serum antibodies.
Main Results:
- CneF-CFA immunization induced CD4+ T cells mediating delayed-type hypersensitivity (DTH) and amplified DTH responses, leading to significantly better protection.
- HKC immunization induced CD4+ and CD8+ T cells involved in DTH and direct killing, but offered no significant protection compared to controls.
- Protection correlated with the presence of T cells responsible for DTH reactivity and/or DTH response amplification, producing gamma interferon and interleukin 2.
- Neither protocol induced protective serum antibodies to glucuronoxylmannan.
Conclusions:
- The CneF-CFA immunization protocol induces a protective T-cell profile against Cryptococcus neoformans.
- Protective immunity is mediated by specific CD4+ T-cell subsets involved in DTH and DTH amplification.
- Cell-mediated immune responses to C. neoformans can be either protective or nonprotective, underscoring the complexity of antifungal immunity.