Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 197, Issue 11, Pages 1405-1416Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20030109
Keywords
immunity; T cells; CD4 help; fungi; AIDS
Categories
Funding
- NIAID NIH HHS [R01 AI034361, AI40996, R01 AI035681, AI34361, R37 AI035681, AI35681, AI42747, R01 AI040996] Funding Source: Medline
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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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