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Infection and Immunity, October 2001, p. 6445-6455, Vol. 69, No. 10
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.10.6445-6455.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Both Th1 and Th2 Cytokines Affect the Ability of
Monoclonal Antibodies To Protect Mice against Cryptococcus
neoformans
David O.
Beenhouwer,1,2,
Scott
Shapiro,1
Marta
Feldmesser,2
Arturo
Casadevall,2,3 and
Matthew D.
Scharff1,*
Departments of Cell
Biology,1
Medicine,2 and Microbiology and
Immunology,3 Albert Einstein College of
Medicine, Bronx, New York 10461
Received 29 March 2001/Returned for modification 10 May
2001/Accepted 28 June 2001
Variable-region-identical mouse immunoglobulin G1 (IgG1), IgG2b,
and IgG2a monoclonal antibodies to the capsular polysaccharide of
Cryptococcus neoformans prolong the lives of mice
infected with this fungus, while IgG3 is either not protective or
enhances infection. CD4+ T cells are required for
IgG1-mediated protection, and CD8+ T cells are required for
IgG3-mediated enhancement. Gamma interferon is required for both
effects. These findings revealed that T cells and cytokines play a role
in the modulation of cryptococcal infection by antibodies and suggested
that it was important to more fully define the cytokine requirements of
each of the antibody isotypes. We therefore investigated the efficacy
of passively administered variable-region-identical IgG1, IgG2a, IgG2b,
and IgG3 monoclonal antibodies against intravenous infection with
C. neoformans in mice genetically deficient in
interleukin-12 (IL-12), IL-6, IL-4, or IL-10, as well as in the
parental C57BL/6J strain. The relative inherent susceptibilities of
these mouse strains to C. neoformans were as follows:
IL-12
/
> IL-6
/
> C57BL/6J
IL-4
/
IL-10
/
.
This is consistent with the notion that a Th1 response is necessary for
natural immunity against cryptococcal infection. However, none of the
IgG isotypes prolonged survival in IL-12
/
,
IL-6
/
, or IL-4
/
mice, and all isotypes
significantly enhanced infection in IL-10
/
mice. These
results indicate that passive antibody-mediated protection against
C. neoformans requires both Th1- and Th2-associated
cytokines and reveal the complexity of the mechanisms through which
antibodies modulate infection with this organism.
*
Corresponding author. Mailing address: Department of
Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park
Ave., Bronx, NY 10461. Phone: (718) 430-3527. Fax: (718) 430-8574. E-mail: scharff{at}aecom.yu.edu.

Present address: University of California Los Angeles, Department
of Microbiology, Immunology and Molecular Genetics, Los
Angeles, CA
90025-1489.
Infection and Immunity, October 2001, p. 6445-6455, Vol. 69, No. 10
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.10.6445-6455.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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