Cited by 72Fungal Infections and StudiesImmune responses and vaccinationsBacterial Infections and Vaccines

Protective Immunity against Experimental Pulmonary Cryptococcosis in T Cell-Depleted Mice

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Wozniak, Karen L., Young, Mattie L., Wormley, Floyd L.·2011·Clinical and Vaccine Immunology

Abstract

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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Registry

Crossref · 10.1128/cvi.00036-11

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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.”
  • 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.”

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Authors
Wozniak, K. L., Young, M. L., & Wormley, F. L.
Affiliations
The University of Texas at San Antonio (US)
Venue
Clinical and Vaccine Immunology
Published
2011-03-30
Volume
18
Issue
5
Pages
717-723
ISSN
  • 1556-679X (ISSN-L)
  • 1556-6811
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
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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