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Infection and Immunity, September 1998, p. 4440-4449, Vol. 66, No. 9
Department of
Dermatology,1
Cancer
Center,2
Strong Children's Research
Center,3 and
Department of Microbiology
and Immunology,4 University of Rochester School
of Medicine and Dentistry, Rochester, New York 14642
Received 3 March 1998/Returned for modification 7 May 1998/Accepted 24 June 1998
Transgenic (Tg) mice whose epidermal keratinocytes constitutively
overexpress either B7-1 (CD80) or B7-2 (CD86) exhibited exaggerated
cutaneous delayed type hypersensitivity (DTH) to haptens compared to
non-Tg mice. To determine whether enhanced DTH in these Tg mice is seen
in response to cutaneous fungal infections, a primary infection with
Candida albicans was established by inoculating this
organism on the occluded skin of Tg and non-Tg mice. These infections
resolved 7 days after removal of occlusive dressing in all three groups
of mice, without evidence of exaggerated inflammation in either the Tg
or non-Tg mice. Only B7-2 Tg mice developed enhanced Th1-lymphocyte-mediated immune responses to C. albicans antigens after resolving this infection: enhanced
footpad swelling in response to intradermal C. albicans antigens, enhanced production of mRNA encoding Th1
lymphokines in draining lymph nodes, and increased gamma interferon
secreted into culture supernatants by lymph node T lymphocytes
stimulated with Candida antigens in vitro. Lastly, Western
blotting of sera from mice that had resolved this fungal infection
indicated that only B7-2 Tg mice recognized a wide range of
Candida-associated antigens. These data suggest that these two costimulatory molecules, when expressed by keratinocytes, do not
deliver identical signals to C. albicans
antigen-reactive Th1 lymphocytes. The enhanced immune response in B7-2
Tg mice to a cutaneous C. albicans infection
demonstrates the importance of antigen presentation and
costimulation in immune reactivity to fungi. Furthermore, B7-2 Tg mice
may be useful in identification of protective Candida
antigens.
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
CD86 (B7-2), but Not CD80 (B7-1), Expression in the Epidermis of
Transgenic Mice Enhances the Immunogenicity of Primary Cutaneous
Candida albicans Infections


*
Corresponding author. Mailing address: 601 Elmwood
Ave., Box 697, Rochester, NY 14642. Phone: (716) 275-1802. Fax: (716)
271-4715. E-mail: Anthony_Gaspari{at}urmc.rochester.edu.
Present address: Department of Dermatology, University of North
Carolina
Chapel Hill, Chapel Hill, NC.
Present address: Department of Hematology, Columbia University,
New York, NY.
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