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Infection and Immunity, March 2001, p. 1508-1514, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1508-1514.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Cytotoxic T Lymphocyte Antigen Costimulation Influences T-Cell Activation in Response to Cryptococcus neoformans

Donatella Pietrella, Stefano Perito, Francesco Bistoni, and Anna Vecchiarelli*

Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy

Received 16 June 2000/Returned for modification 4 August 2000/Accepted 12 December 2000

The kinetics of cytotoxic T lymphocyte antigen 4 (CTLA-4) expression on T cells responding to Cryptococcus neoformans and its role in regulating the T-cell response were examined. Using peripheral blood mononuclear cells stimulated with encapsulated or acapsular C. neoformans we showed that (i) the encapsulated strain augmented CTLA-4 expression on the T-cell surface while the acapsular strain was a weaker modulator, (ii) CTLA-4 molecules were rapidly up-regulated after the addition of encapsulated C. neoformans, (iii) CTLA-4 was up-regulated predominantly in CD4+ T cells responding to C. neoformans, and (iv) blockage of CTLA-4 with (Fab')2 of monoclonal antibody to CTLA-4 induced T-cell proliferation that paralleled the enhancement of interleukin-2 and gamma interferon production. These results suggest that capsular material, the major virulence factor of C. neoformans, promotes synthesis and expression of CTLA-4 molecules predominantly in CD4+ T cells. CTLA-4-mediated deactivation is due not to lack of costimulation but to specific recognition of CTLA-4 for B7 molecules. This appears to be a new mechanism by which C. neoformans may elude the host immune response.

* Corresponding author. Mailing address: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. Phone: 39-075-585-7407. Fax: 39-075-585-7403. E-mail: vecchiar{at}unipg.it.

Infection and Immunity, March 2001, p. 1508-1514, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1508-1514.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Vecchiarelli, A., Pietrella, D., Lupo, P., Bistoni, F., McFadden, D. C., Casadevall, A. (2003). The polysaccharide capsule of Cryptococcus neoformans interferes with human dendritic cell maturation and activation. J. Leukoc. Biol. 74: 370-378 [Abstract] [Full Text]  
  • Humphreys, I. R., Edwards, L., Walzl, G., Rae, A. J., Dougan, G., Hill, S., Hussell, T. (2003). OX40 Ligation on Activated T Cells Enhances the Control of Cryptococcus neoformans and Reduces Pulmonary Eosinophilia. J. Immunol. 170: 6125-6132 [Abstract] [Full Text]  


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