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Infection and Immunity, September 1999, p. 4620-4627, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The Capsule of Cryptococcus neoformans Reduces T-Lymphocyte Proliferation by Reducing Phagocytosis, Which Can Be Restored with Anticapsular Antibody

Rachel M. Syme,1 Tony F. Bruno,1 Thomas R. Kozel,2 and Christopher H. Mody1,3,*

Department of Microbiology and Infectious Diseases1 and Department of Internal Medicine,3 University of Calgary, Calgary, Alberta, Canada T2N 4N1, and Department of Microbiology, University of Nevada, Reno, Nevada 595572

Received 28 December 1998/Returned for modification 27 January 1999/Accepted 3 June 1999

Cell-mediated immunity is critical for the host defense to Cryptococcus neoformans, as demonstrated by numerous animal studies and the prevalence of the infection in AIDS patients. Previous studies have established that the polysaccharide capsule contributes to the virulence of C. neoformans by suppressing T-lymphocyte proliferation, which reflects the clonal expansion of T lymphocytes that is a hallmark of cell-mediated immunity. The present studies were performed to identify the major mechanism by which polysaccharide impairs lymphocyte proliferation, since capsular polysaccharide has the potential to affect the development of T-lymphocyte responses by stimulating production of interleukin-10 (IL-10), inhibiting phagocytosis, and inducing shedding of cell surface receptors. We demonstrate that polysaccharide inhibits lymphocyte proliferation predominantly by blocking uptake of C. neoformans, which is crucial for subsequent lymphocyte proliferation. In addition, we show that polysaccharide did not suppress lymphocyte proliferation via an IL-10-dependent mechanism, nor did it affect critical surface receptor interactions on the T cell or antigen-presenting cell. Having established that polysaccharide impairs phagocytosis, we performed studies to determine whether opsonization with human serum or with anticapsular antibody could reverse this effect. Impaired uptake and lymphocyte proliferation that were induced by polysaccharide can be enhanced through opsonization with monoclonal antibodies or human serum, suggesting that antipolysaccharide antibodies might enhance the host defense by restoring uptake of the organism and subsequent presentation to T lymphocytes. These studies support the therapeutic potential of stimulating cell-mediated immunity to C. neoformans with anticapsular antibody.

* Corresponding author. Mailing address: Division of Pulmonary Medicine, Room 273, Heritage Medical Research Building, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta, Canada T2N 4N1. Phone: (403) 220-5979. Fax: (403) 270-2772. E-mail: cmody{at}ucalgary.ca.

Infection and Immunity, September 1999, p. 4620-4627, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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