Protective Immunity against Experimental Pulmonary Cryptococcosis in T Cell-Depleted Mice
Open accessAbstract
Individuals with defects in T cell-mediated immunity (CMI) are highly susceptible to infection with Cryptococcus neoformans. The purpose of these studies was to determine if protection against experimental pulmonary cryptococcosis can be generated in T cell-deficient hosts. BALB/c mice were depleted of CD4+and/or CD8+T cells or given an isotype control antibody prior to vaccination with a C. neoformans strain, designated H99γ, previously shown to induce protection against C. neoformans infection in immunocompetent mice. Mice depleted of CD4+or CD8+T cells, but not both subsets, survived an acute pulmonary infection with C. neoformans strain H99γ and a subsequent second challenge with wild-type C. neoformans strain H99. We observed a significant increase in the percentage of CD4+and CD8+T cells expressing the activation marker CD69 in the lungs of mice immunized with C. neoformans strain H99γ prior to a secondary challenge with wild-type cryptococci. CD4+T cells within the lungs of immunized mice also appeared to acquire a predominantly activated effector memory cell phenotype (CD69+CD44+CCR7−CD45RB−CD62L−) following a second pulmonary challenge with wild-type C. neoformans, compared to CD4+T cells from naïve mice. Lastly, immunization of immunocompetent mice with C. neoformans strain H99γ prior to depletion of CD4+and/or CD8+T cells resulted in significant protection against a second challenge with wild-type C. neoformans. Our studies demonstrate that protective immunity against pulmonary cryptococcosis can be generated in immunosuppressed hosts, thus supporting the development of cryptococcal vaccines.
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Immunocompetent mice immunized with H99γ and subsequently depleted of both CD4+ and CD8+ T cells were protected upon challenge with wild-type C. neoformans.
“Furthermore, immunocompetent mice immunized with H99γ that were subsequently depleted of both CD4+ T cells and CD8+ T cells were protected upon challenge with wild-type C. neoformans133.”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [133]
Immunization with a C. neoformans strain genetically engineered to produce IFNγ (H99γ) induced protective immunity in mice depleted of CD4+ T cells.
“Interestingly, in a mouse model of cryptococcosis, immunization with a C. neoformans strain that was genetically engineered to produce IFNγ (H99γ) induced protective immunity in mice depleted of CD4+ T cells133,134.”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [133]
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Self-citation
- Authors
- Wozniak, K. L., Young, M. L., & Wormley, F. L.
- Affiliations
- The University of Texas at San Antonio (US)
- Venue
- Clinical and Vaccine Immunology
- Publisher
- American Society for Microbiology
- Published
- 2011-03-30
- Volume
- 18
- Issue
- 5
- Pages
- 717-723
- ISSN
- 1556-679X (ISSN-L)
- 1556-6811
- PMC
- PMC3122518
- OpenAlex
- W2132724051
- Cited by
- 72
- References
- 42
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2023: 8 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 7 · 2016: 7 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 8
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Clinical and Vaccine Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI071752, RO1AI071752)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Keywords
- pulmonary cryptococcosis, Cryptococcus neoformans, T cell depletion, CD4+ T cells, CD8+ T cells, T cell immunity, CD69, effector memory T cells, secondary challenge, immunocompromised patients
- MeSH terms
- Animals, Cryptococcosis, Cryptococcus neoformans, Female, Lung Diseases, Fungal, Lymphocyte Depletion, Mice, Inbred BALB C, T-Lymphocytes, Survival Analysis, Mice
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