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Infect Immun, May 1998, p. 2107-2114, Vol. 66, No. 5
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Expansion of Vgamma 9Vdelta 2 T Cells Is Triggered by Francisella tularensis-Derived Phosphoantigens in Tularemia but Not after Tularemia Vaccination

Yannick Poquet,1 Michal Kroca,2,3 Franck Halary,4 Stephan Stenmark,3 Marie-Alix Peyrat,4 Marc Bonneville,4 Jean Jacques Fournié,1 and Anders Sjöstedt3,5,*

INSERM U395 and IFR 30, CHU Purpan, Toulouse 31024,1 and INSERM U463, Institut de Biologie, Nantes 44035,4 France; Institute of Immunology, PMMA, 500 01 Hradec Kralove, Czech Republic2; and Department of Infectious Diseases, Umeå University, S-901 87 Umeå,3 and Department of Microbiology, Defence Research Establishment, S-901 82 Umeå,5 Sweden

Received 3 September 1997/Returned for modification 20 October 1997/Accepted 16 February 1998

Tularemia is a disease caused by the facultative intracellular bacterium Francisella tularensis. Here we demonstrate that during the first weeks of infection, a significant increase in levels of Vgamma 9Vdelta 2 cells occurred in peripheral blood: in 13 patients analyzed 7 to 18 days after the onset of disease, these lymphocytes represented, on average, 30.5% of CD3+ cells and nearly 100% of gamma delta + T cells. By contrast, after vaccination with the live vaccine strain (LVS) of F. tularensis, only a minor increase occurred. Eleven days after vaccination, gamma delta T cells represented an average of 6.7% and Vgamma 9Vdelta 2 cells represented an average of 5.3% of T cells, as in control subjects. Since derivatives of nonpeptidic pyrophosphorylated molecules, referred to as phosphoantigens, are powerful stimuli for Vgamma 9Vdelta 2 cells, this observation prompted an investigation of phosphoantigens in F. tularensis strains. The F. tularensis phosphoantigens triggered in vitro a proliferative response of human Vgamma 9Vdelta 2 peripheral blood leukocytes as well as a cytotoxic response and tumor necrosis factor release from a Vgamma 9Vdelta 2 T-cell clone. Quantitatively similar phosphoantigenic activity was detected in acellular extracts from two clinical isolates (FSC171 and Schu) and from LVS. Taken together, the chemical nature of the stimulus from the clinical isolates and the significant increase in levels of Vgamma 9Vdelta 2 cells in peripheral blood of tularemia patients indicate that phosphoantigens produced by virulent strains of F. tularensis trigger in vivo expansion of gamma delta T cells in tularemia.

* Corresponding author. Mailing address: Department of Microbiology, Defence Research Establishment, S-901 82 Umeå, Sweden. Phone: 46-90-106665. Fax: 46-90-106806. E-mail: sjostedt{at}ume.foa.se.

Infect Immun, May 1998, p. 2107-2114, Vol. 66, No. 5
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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