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Infection and Immunity, February 2001, p. 665-672, Vol. 69, No. 2
Department of Pathology, College of
Veterinary Medicine and Biomedical Sciences, Colorado State
University, Fort Collins, Colorado 80523
Received 30 June 2000/Returned for modification 4 September
2000/Accepted 24 October 2000
The importance of CD40, CD80, and CD86 costimulatory molecules in
anti-Leishmania immune responses has been established in murine models. A role for these costimulatory molecules in human anti-Leishmania immune responses was investigated in this
study. Autologous macrophages and peripheral blood leukocytes (PBL)
were prepared from peripheral blood mononuclear cells of
Leishmania-naive donors and cultured with or without
Leishmania major in various combinations. After 7 days of
culture, high levels of CD40 and CD86 were expressed on macrophages in
the presence or absence of L. major. When macrophages were
cultured for an additional 7 days with PBL, expression of all three
costimulatory molecules was detected. When L. major was
present in these cultures, the expression of CD80, and to a lesser
extent CD40, on macrophages was enhanced. Blockade of CD80, CD86, or
both molecules (in the order of greatest effect) in cultures containing
macrophages, PBL, and L. major significantly inhibited the
production of gamma interferon, interleukin-5 (IL-5), and IL-12.
Blockade of CD40-CD154 interactions also significantly inhibited
production of these cytokines in response to L. major.
Production of IL-10 was unaltered by the blockade of these
costimulatory molecules. Thus, these data suggest that CD40, CD80, and
CD86 expression and regulation may significantly impact
anti-Leishmania immune responses in humans.
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.2.665-672.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Influence of Costimulatory Molecules on Immune
Response to Leishmania major by Human Cells In
Vitro

*
Corresponding author. Mailing address: Department of
Pathology, College of Veterinary Medicine and Biomedical Sciences,
Colorado State University, Fort Collins, CO 80523. Phone: (970)
491-4964. Fax: (970) 491-0603. E-mail:
rtitus{at}cvmbs.colostate.edu.
Present address: Laboratório de Imunologia, Departamento de
Biointeração, Instituto de Ciências da Saúde,
Universidade Federal da Bahia, Salvador, Bahia, Brazil.
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