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Infection and Immunity, January 2002, p. 335-344, Vol. 70, No. 1
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.1.335-344.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Neisserial Immunoglobulin A1 Protease Induces Specific T-Cell Responses in Humans

Anastasios Tsirpouchtsidis,¹ Robert Hurwitz,¹ Volker Brinkmann,² Thomas F. Meyer,^1* and Gaby Haas¹

Abteilung Molekulare Biologie,¹ Zentralbereich Mikroskopie, Max-Planck-Institut für Infektionsbiologie, D-10117 Berlin, Germany²

Received 6 July 2001/ Returned for modification 28 August 2001/ Accepted 19 October 2001

We have previously shown that immunoglobulin A1 (IgA1) protease, an exoenzyme of pathogenic neisseriae, can trigger the release of proinflammatory cytokines from human monocytic subpopulations. Here, we demonstrate a dose-dependent T-cell response to recombinant gonococcal IgA1 protease (strain MS11) in healthy human blood donors. This response was delayed in comparison to the immune response against tetanus toxoid. Stimulation with IgA1 protease led to the activation of CD4⁺ and CD8⁺ T cells, as well as CD19⁺ B cells and CD56⁺ NK cells, indicated by de novo expression of CD69. Only CD4⁺ T cells proliferated and stained positive for intracellular gamma interferon (IFN-). Both proliferation and IFN- production were dependent on antigen presentation via major histocompatibility complex class II. Peripheral blood mononuclear cells stimulated with IgA1 protease produce IFN- and tumor necrosis factor alpha but no, or very low amounts of, interleukin-10 (IL-10) or IL-4, indicating a Th1-based proinflammatory immune response. These findings support the significance of IgA1 protease as a virulence determinant of bacterial meningitis and its function as a dominant proinflammatory T-cell antigen.

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* Corresponding author. Mailing address: Abteilung Molekulare Biologie, Max-Planck-Institut für Infektionsbiologie, Schumannstrasse 21/22, D-10117 Berlin, Germany. Phone: 49 30 2846 0400. Fax: 49 30 2846 0401. E-mail: meyer{at}mpiib-berlin.mpg.de.

Editor: E. I. Tuomanen

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Infection and Immunity, January 2002, p. 335-344, Vol. 70, No. 1
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.1.335-344.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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