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Infect Immun, June 1998, p. 2632-2639, Vol. 66, No. 6
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.
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
*
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.
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