Vaccines and cell-mediated immunity.

In a previous study we demonstrated that Salmonella typhimurium-induced immunosuppression involved T-cell non-responsiveness to interleukin-2 (IL-2). In this study we observed that Salmonella-induced T-cell non-responsiveness to IL-2 was not reversed completely by treatment with N(G)-monomethyl-L-arginine, which is known to inhibit nitric oxide (NO) secretion by macrophages in culture. Furthermore, when purified splenic T-lymphocytes from Salmonella-infected mice were activated with an anti-CD3 antibody, the responsiveness of these T-cells to IL-2 was suppressed significantly. Results of flow cytometric analysis using an anti-IL-2 receptor gamma chain (IL-2Rgamma) antibody showed that IL-2Rgamma expression in mitogen-activated T-cells was down-regulated by Salmonella infection. These results suggest that Salmonella infection-induced T-cell non-responsiveness to IL-2 involves a defective function of T-cells themselves and appears to be regulated by inhibition of IL-2Rgamma expression in T-cells.

Section: Introductionmentioning

confidence: 99%

Salmonella infection-induced non-responsiveness of murine splenic T-lymphocytes to interleukin-2 (IL-2) involves inhibition of IL-2 receptor γ chain expression

Matsui¹

1998

Section: Introductionmentioning

confidence: 99%

A cell-free extract of Salmonella typhimurium inhibits mitogen-induced proliferation of murine splenic T lymphocytes

Matsui¹

1994

In this study, a cell-free extract of Salmonella inhibited T cell mitogen-induced proliferation of spleen cells from non-immunized mice. The proliferation of murine spleen cells stimulated with a T cell mitogen, such as phytohaemagglutinin (PHA) or concanavalin A (ConA) was suppressed significantly when the cells were treated with a sonicate of S. typhimurium, but not of E. coli. The agent(s) responsible for the suppressive effect existed mainly in the soluble fraction of S. typhimurium, whereas the membrane fraction possessed minimal activity. The T cell proliferation suppression paralleled the level of interleukin-2 (IL-2) secretion. Addition of phorbol 12-myristate-13 acetate (PMA) to the cultures restored IL-2 secretion to normal levels, although proliferation remained suppressed and was not reversed by treatment with recombinant IL-2. These results suggest that the suppression of T cell proliferation induced by a soluble Salmonella fraction is associated with inhibition of IL-2 secretion and the response of T cells to IL-2 and the former effect is dependent upon the inhibition of the stimulatory activity of protein kinase C on IL-2 secretion. This type of suppression may explain a mechanism of immunosuppression induced by murine typhoid fever.

“…Salmonella typhimurium is a facultative intracellular pathogen that causes systemic infection in mice [1]. The host defense in murine salmonellosis, a model system of human typhoid fever, involves both hu-moral and cellular immune responses [2,3].…”

Section: Introductionmentioning

confidence: 99%

DNA sequencing of the gene encoding Salmonella typhimurium-derived T-cell inhibitor (STI) and characterization of the gene product, cloned STI

Matsui¹

1998

In a previous study, we found a novel protein which inhibited T-cell responsiveness to interleukin-2 (IL-2) in Salmonella typhimurium and called it S. typhimurium-derived T-cell inhibitor (STI). In this study, we analyzed the DNA sequence of the gene encoding STI. The STI gene was cloned into a plasmid vector, pUC118, and expressed in Escherichia coli JM109. Like native STI, the cloned STI inhibited IL-2-dependent CTLL-2 cell growth. Furthermore, this growth inhibition involved down-regulation of IL-2 receptor expression. These results indicate that the cloned STI expressed in E. coli was identical to native STI. Sequencing revealed that the STI gene contained an open reading frame of 2298 base pairs encoding a precursor form of 765 amino acid residues (molecular mass 83605) that is processed into a mature form of 745 amino acid residues with molecular mass 81 548. Homology analysis revealed that its amino acid sequence was highly homologous with that of the beta-glucosidase of E. coli K-12. We designated the gene encoding STI sti.