The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 2 June 2003. doi:10.1084/jem.20030109
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 163K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wüthrich, M.
Right arrow Articles by Klein, B. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wüthrich, M.
Right arrow Articles by Klein, B. S.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© Rockefeller University Press, 0022-1007/2003/6/1405 $5.00
The Journal of Experimental Medicine, Volume 197, Number 11, 1405-1416

Vaccine Immunity to Pathogenic Fungi Overcomes the Requirement for CD4 Help in Exogenous Antigen Presentation to CD8+ T Cells : Implications for Vaccine Development in Immune-deficient Hosts



Marcel Wüthrich1, Hanna I. Filutowicz1, Tom Warner2, George S. Deepe, Jr.6 and Bruce S. Klein1,3,4,5

1 Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI 53792
2 Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI 53792
3 Department of Internal Medicine, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI 53792
4 Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI 53792
5 The Comprehensive Cancer Center, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI 53792
6 Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267

Address correspondence to Dr. Bruce S. Klein, University of Wisconsin Hospitals and Clinics, 600 Highland Ave., K4/434, Madison, WI 53792. Phone: 608-263-9217; Fax: 608-263-0440; E-mail: bsklein{at}facstaff.wisc.edu

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.

Key Words: immunity • T cells • CD4 help • fungi • AIDS


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS