Abstract |
Systemic fungal infections with primary and opportunistic pathogens have become increasingly common and represent a growing health menace in patients with AIDS and other immune deficiencies. T lymphocyte immunity, in particular the CD4+ Th 1 cells, is considered the main defense against these pathogens, and their absence is associated with increased susceptibility. It would seem illogical then to propose vaccinating these vulnerable patients against fungal infections. We report here that CD4+ T cells are dispensable for vaccine-induced resistance against experimental fungal pulmonary infections with two agents, Blastomyces dermatitidis an extracellular pathogen, and Histoplasma capsulatum a facultative intracellular pathogen. In the absence of T helper cells, exogenous fungal antigens activated memory CD8+ cells in a major histocompatibility complex class I-restricted manner and CD8+ T cell-derived cytokines tumor necrosis factor alpha, interferon gamma, and granulocyte/macrophage colony-stimulating factor-mediated durable vaccine immunity. CD8+ T cells could also rely on alternate mechanisms for robust vaccine immunity, in the absence of some of these factors. Our results demonstrate an unexpected plasticity of immunity in compromised hosts at both the cellular and molecular level and point to the feasibility of developing vaccines against invasive fungal infections in patients with severe immune deficiencies, including those with few or no CD4+ T cells.
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Authors | Marcel Wuthrich, Hanna I Filutowicz, Tom Warner, George S Deepe Jr, Bruce S Klein |
Journal | The Journal of experimental medicine
(J Exp Med)
Vol. 197
Issue 11
Pg. 1405-16
(Jun 02 2003)
ISSN: 0022-1007 [Print] United States |
PMID | 12782709
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- CD4 Antigens
- Fungal Vaccines
- Histocompatibility Antigens Class I
- Tumor Necrosis Factor-alpha
- Interferon-gamma
- Granulocyte-Macrophage Colony-Stimulating Factor
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Topics |
- Animals
- Antigen Presentation
- Blastomyces
(immunology, pathogenicity)
- Blastomycosis
(immunology, prevention & control)
- CD4 Antigens
(genetics)
- CD4-Positive T-Lymphocytes
(immunology)
- CD8-Positive T-Lymphocytes
(immunology)
- Fungal Vaccines
(immunology, pharmacology)
- Granulocyte-Macrophage Colony-Stimulating Factor
(biosynthesis)
- Histocompatibility Antigens Class I
(metabolism)
- Histoplasma
(immunology, pathogenicity)
- Histoplasmosis
(immunology, prevention & control)
- Interferon-gamma
(biosynthesis)
- Lung
(immunology)
- Lung Diseases, Fungal
(immunology, prevention & control)
- Mice
- Mice, Congenic
- Mice, Inbred C57BL
- Mice, Knockout
- Tumor Necrosis Factor-alpha
(biosynthesis)
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