CHANGES IN THE PERIPHERAL-BLOOD T-CELL RECEPTOR V-BETA REPERTOIRE IN-VIVO AND IN-VITRO DURING SHIGELLOSIS

A sequential activation of T cells in peripheral blood during shigello sis has been observed (D. Islam, P. K, Bardhan, A. A. Lindberg, and B. Christensson, Infect, Immun. 63:2941-2949, 1995), To further investig ate the cellular response during the course of Shigella infection, cha nges in the T-cell receptor (TCR) repertoire in the peripheral blood w ere analyzed, The hypothesis for monitoring changes in the TCR V beta repertoire of T-cell subsets in blood in patients during shigellosis w as that Shigella antigens may modulate the function of T cells carryin g TCRs capable of recognizing Shigella-specific epitopes or superantig ens. Such a selective preference for T cells expressing certain TCR V beta types could lead to the expansion or deletion of these T cells, I n the present study of 27 adult male Bangladeshi patients with dysente ry (14 cases caused by Shigella dysenteriae 1 and 13 cases caused by S higella flexneri), the changes in the TCR V beta repertoire of periphe ral blood CD4(+) and CD8(+) T-cell subsets have been analyzed with a p anel of nine anti-Vp monoclonal antibodies by how cytometry, Twenty he althy 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 V beta 2, V beta 3, and V beta 17, with a maximum at day 7 after the onset of disease, The frequency of CD4(+) T cells expressing V beta 5.1 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 V beta-specific manner, Stimulation with heat-killed S. dysenteri ae 1 and Shiga toxin enhanced the frequency of cells expressing V beta 2, V beta 3, V beta 5.1, V beta 13.6, and V beta 17, especially in sa mples obtained at day 7, The enhanced frequency of cells expressing V beta 2, V beta 3, V beta 5.1, and V beta 17 found both in in vivo and in vitro could suggest that in shigellosis antigens or superantigens a re presented to the immune system and preferentially activate certain TCR V beta types in T-cell subsets, The kinetics of the change in the TCR V beta repertoire in blood during shigellosis may indicate that fo llowing local activation, the antigen activated T cells can be retriev ed in the blood and restimulated in vitro, If confirmed by parallel an alysis of T cells in the gut and blood by TCR sequence analysis, the p ossibility 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.