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Infection and Immunity, January 2007, p. 193-200, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01148-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Vß1+ Jß1.1+/V{alpha}2+ J{alpha}49+ CD4+ T Cells Mediate Resistance against Infection with Blastomyces dermatitidis{triangledown}

Marcel Wüthrich,1* Hanna I. Filutowicz,1 Holly L. Allen,2 George S. Deepe,2 and Bruce S. Klein1,3,4,5

Departments of Pediatrics,1 Internal Medicine,3 Medical Microbiology and Immunology,4 Comprehensive Cancer Center, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53792,5 Division of Infectious Diseases, University of Cincinnati College of Medicine and Veterans Affairs Hospital, Cincinnati, Ohio 452672

Received 21 July 2006/ Returned for modification 16 September 2006/ Accepted 30 September 2006

Immunization with a cell wall/membrane (CW/M) and yeast cytosol extract (YCE) crude antigen from Blastomyces dermatitidis confers T-cell-mediated resistance against lethal experimental infection in mice. We isolated and characterized T cells that recognize components of these protective antigens and mediate protection. CD4+ T-cell clones elicited with CW/M antigen adoptively transferred protective immunity when they expressed a V{alpha}2+ J{alpha}49+/Vß1+ Jß1.1+ heterodimeric T-cell receptor (TCR) and produced high levels of gamma interferon (IFN-{gamma}). In contrast, Vß8.1/8.2+ CD4+ T-cell clones that were reactive against CW/M and YCE antigens and produced little or no IFN-{gamma} either failed to mediate protection or exacerbated the infection depending on the level of interleukin-5 expression. Thus, the outgrowth of protective T-cell clones against immunodominant antigens of B. dermatitidis is biased by a combination of the TCR repertoire and Th1 cytokine production.

* Corresponding author. Mailing address: University of Wisconsin Hospitals and Clinics, 600 Highland Ave., K4/444, Madison, WI 53792. Phone: (608) 263-6203. Fax: (608) 263-0722. E-mail: mwuethri{at}wisc.edu.

{triangledown} Published ahead of print on 9 October 2006.

Editor: A. Casadevall

Infection and Immunity, January 2007, p. 193-200, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01148-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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