Changes in the peripheral blood T-cell receptor Vβ repertoire in vivo and in vitro during shigellosis

Abstract

A sequential activation of T cells in peripheral blood during shigellosis has been observed (D. Islam, P. K. Bardhan, A. A. Lindberg, and B. Christensson, Infect. Immun. 63:2941-2949, 1995). To further investigate the cellular response during the course of Shigella infection, changes in the T- cell receptor (TCR) repertoire in the peripheral blood were analyzed. The hypothesis for monitoring changes in the TCR Vβ repertoire of T-cell subsets in blood in patients during shigellosis was that Shigella antigens may modulate the function oft cells carrying TCRs capable of recognizing Shigella-specific epitopes or superantigens. Such a selective preference for T cells expressing certain TCR Vβ types could lead to the expansion or deletion of these T cells. In the present study of 27 adult male Bangladeshi patients with dysentery (14 cases caused by Shigella dysenteriae 1 and 13 cases caused by Shigella flexneri), the changes in the TCR Vβ repertoire of peripheral blood CD4+ and CD8+ T-cell subsets have been analyzed with a panel of nine anti-Vβ monoclonal antibodies by flow cytometry. Twenty healthy males from Bangladesh and 20 healthy males from Sweden served as controls. Compared with the Bangladeshi controls, the patients had an increased frequency of CD4+ T cells expressing Vβ2, Vβ3, and Vβ17, with a maximum at day 7 after the onset of disease. The frequency of CD4+ T cells expressing Vβ5.1 was increased only in patients with S. flexneri infection. Peripheral blood T cells from Shigella-infected patients also responded to in vitro stimulation in a TCR Vβ-specific manner. Stimulation with heat-killed S. dysenteriae 1 and Shiga toxin enhanced the frequency of cells expressing Vβ2, Vβ3, Vβ5.1, Vβ13.6, and Vβ17, especially in samples obtained at day 7. The enhanced frequency of cells expressing Vβ2, Vβ3, Vβ5.1, and Vβ17 found both in in vivo and in vitro could suggest that in shigellosis antigens or superantigens are presented to the immune system and preferentially activate certain TCR Vβ types in T-cell subsets. The kinetics of the change in the TCR Vβ repertoire in blood during shigellosis may indicate that following local activation, the antigen-activated T cells can be retrieved in the blood and restimulated in vitro. If confirmed by parallel analysis oft cells in the gut and blood by TCR sequence analysis, the possibility suggested by our findings would facilitate further analysis of the role of cell-mediated immune responses in the pathogenesis of and protection against Shigella infection.