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Infection and Immunity, November 2000, p. 6147-6153, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Phagocytosis and Protein Processing Are Required for Presentation of Cryptococcus neoformans Mitogen to T Lymphocytes

Rachel M. Syme,1 Jason C. L. Spurrell,1 Ling Ling Ma,2 Francis H. Y. Green,3 and Christopher H. Mody1,4,*

Department of Microbiology and Infectious Diseases,1 Department of Medical Sciences,2 Department of Pathology,3 and Department of Internal Medicine,4 University of Calgary, Calgary, Alberta, Canada

Received 5 April 2000/Returned for modification 27 June 2000/Accepted 7 August 2000

In addition to eliciting antigen specific T-cell-mediated immunity, Cryptococcus neoformans possesses a mitogen (CnM) that activates naive T cells to proliferate. This mechanism of T-cell activation is accessory cell dependent and major histocompatibility complex unrestricted. CnM-induced T-cell proliferation correlates with internalization of the organism, suggesting that intracellular processing is required to liberate CnM prior to presentation to T cells. To determine whether phagocytosis and processing are required, various inhibitors of accessory cell uptake and processing were used. C. neoformans was observed within the accessory cells. Paraformaldehyde fixation of the accessory cell abrogated presentation of CnM to T cells, indicating that a dynamic accessory cell surface was required. A lysosomotropic agent abrogated the response to CnM but had no effect on a control stimulus that did not require processing. Both aspartic acid and cysteine protease inhibitors blocked effective processing of CnM, so that it was unable to stimulate T cells. Finally, an inhibitor of microfilament polymerization abrogated proliferation to CnM. These results indicate that the mitogenic activity of C. neoformans requires phagocytosis of the organism, lysosomal or endosomal processing, proteolytic activity, and microfilament polymerization and intracellular transport as a prerequisite for T-cell proliferation.

* Corresponding author. Mailing address: Room 273, Heritage Medical Research Building, 3330 Hospital Dr. NW, Calgary, Alberta, Canada T2N 4N1. Phone: (403) 220-5979. Fax: (403) 220-8928. E-mail: cmody{at}ucalgary.ca.

Infection and Immunity, November 2000, p. 6147-6153, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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