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Infect Immun, June 1998, p. 2632-2639, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Antigen-Induced Protective and Nonprotective Cell-Mediated Immune Components against Cryptococcus neoformans

Juneann W. Murphy,1,* Fredda Schafer,1 Arturo Casadevall,2 and Adekunle Adesina3

Department of Microbiology and Immunology1 and Department of Pathology,3 University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, and Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, New York 104612

Received 29 September 1997/Returned for modification 15 December 1997/Accepted 16 March 1998

Mice immunized with two different cryptococcal antigen preparations, one a soluble culture filtrate antigen (CneF) in complete Freund's adjuvant (CFA) and the other heat-killed Cryptococcus neoformans cells (HKC), develop two different profiles of activated T cells. CneF-CFA induces CD4+ T cells responsible for delayed-type hypersensitivity (DTH) reactivity and for amplification of the anticryptococcal DTH response, whereas HKC induce CD4+ and CD8+ T cells involved in anticryptococcal DTH reactivity and activated T cells which directly kill C. neoformans cells. The main purpose of this study was to assess the level of protection afforded by each of the two different T-cell profiles against challenge with viable C. neoformans cells, thereby identifying which activated T-cell profile provides better protection. CBA/J mice immunized with CneF-CFA had significantly better protective responses, based on better clearance of C. neoformans from tissues, on longer survival times, and on fewer and smaller lesions in the brain, than HKC-immunized mice or control mice similarly infected with C. neoformans. Both immunization protocols induced an anticryptococcal DTH response, but neither induced serum antibodies to glucuronoxylmannan, so the protection observed in the CneF-CFA immunized mice was due to the activated T-cell profile induced by that protocol. HKC-immunized mice, which displayed no greater protection than controls, did not have the amplifier cells. Based on our findings, we propose that the protective anticryptococcal T cells are the CD4+ T cells which have been shown to be responsible for DTH reactivity and/or the CD4+ T cells which amplify the DTH response and which have been previously shown to produce high levels of gamma interferon and interleukin 2. Our results imply that there are protective and nonprotective cell-mediated immune responses and highlight the complexity of the immune response to C. neoformans antigens.

* Corresponding author. Mailing address: University of Oklahoma Health Sciences Center, Department of Microbiology and Immunology, P.O. Box 26901, Oklahoma City, OK 73190. Phone: (405) 271-3110. Fax: (405) 271-3117. E-mail: juneann-murphy{at}uokhsc.edu.

Infect Immun, June 1998, p. 2632-2639, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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