Vβ1 + Jβ1.1 + /Vα2 + Jα49 + CD4 + T Cells Mediate Resistance against Infection with Blastomyces dermatitidis

Author:

Wüthrich Marcel1,Filutowicz Hanna I.1,Allen Holly L.2,Deepe George S.2,Klein Bruce S.1345

Affiliation:

1. Departments of Pediatrics

2. Division of Infectious Diseases, University of Cincinnati College of Medicine and Veterans Affairs Hospital, Cincinnati, Ohio 45267

3. Internal Medicine

4. Medical Microbiology and Immunology

5. Comprehensive Cancer Center, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53792

Abstract

ABSTRACT 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 Vα2 + Jα49 + /Vβ1 + Jβ1.1 + heterodimeric T-cell receptor (TCR) and produced high levels of gamma interferon (IFN-γ). In contrast, Vβ8.1/8.2 + CD4 + T-cell clones that were reactive against CW/M and YCE antigens and produced little or no IFN-γ 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.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

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