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Infection and Immunity, August 2006, p. 4538-4548, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.00080-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Diversity of the T-Cell Response to Pulmonary Cryptococcus neoformans Infection

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine,¹ Immunology Graduate Program,² Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan³

Received 16 January 2006/ Returned for modification 24 January 2006/ Accepted 22 April 2006

Cell-mediated immunity plays an important role in immunity to the pathogenic fungus Cryptococcus neoformans. However, the antigen specificity of the T-cell response to C. neoformans remains largely unknown. In this study, we used two approaches to determine the antigen specificity of the T-cell response to C. neoformans. We report here that a diverse T-cell receptor (TCR) Vß repertoire was maintained throughout the primary response to pulmonary C. neoformans infection in immunocompetent mice. CD4⁺ T-cell deficiency resulted in relative expansion of all CD8⁺ T-cell subsets. During a secondary immune response, preferential usage of a TCR Vß subset in CD4⁺ T cells occurred in single individuals, but the preferences were "private" and not shared between individuals. Both CD4⁺ and CD8⁺ T cells from the secondary lymphoid tissues of immunized mice proliferated in response to a variety of C. neoformans antigens, including heat-killed whole C. neoformans, culture filtrate antigen, C. neoformans lysate, and purified cryptococcal mannoprotein. CD4⁺ and CD8⁺ T cells from the secondary lymphoid tissues of mice undergoing a primary response to C. neoformans proliferated in response to C. neoformans lysate. In response to stimulation with C. neoformans lysate, lung CD4⁺ and CD8⁺ T cells produced the effector cytokines tumor necrosis factor alpha and gamma interferon. These results demonstrate that a diverse T-cell response is generated in response to pulmonary C. neoformans infection.

Editor: A. Casadevall