The cellular immune response in rabbits orally immunized with Shigella flexneri.

Abstract

The cellular basis for a mucosal memory response to S. flexneri is described. Rabbits were orally primed and boosted with live avirulent S. flexneri. Single cell suspensions of the Peyer's patch (PP), mesenteric lymph node (MLN), spleen (SPL), and peripheral blood (PB) lymphocytes were cultured for 14 days. Supernatants were collected and analyzed for anti-S. flexneri LPS IgA and IgG. in vitro production of specific IgA by cultured lymphocytes was distributed throughout all four organs. However, cultured PP cells yielded significantly greater amounts of anti-S. flexneri LPS IgA than cells from the MLN, SPL, or PB. Production of specific IgG was rare. Furthermore, it was discovered that the IgA responses in these tissues could be influenced by T cells isolated from the PP. PP lymphocytes were sorted by flow cytometry into separate T and B cell populations and cultured with whole cell preparations of PP, MLN, SPL, and PB. Addition of PP T cells to cultured lymphocytes from the PB and SPL caused a marked increase in the anti-S. flexneri LPS production, which is normally very low or undetectable in these organs. PP T cells suppressed the production of specific IgA in cultured PP cells and caused no change in specific IgA production by MLN lymphocytes. These findings suggest that PP T cells contain memory T helper or T contrasuppressor cells which interact with precursor B cells from the systemic immune compartment to cause preferential differentiation into specific anti-S. flexneri LPS IgA producing cells. T cells sorted from the PP may also cause the expansion of previously committed B cells to specific IgA production. These results reveal a possible role for PP T cells in the regulation of the mucosal immune response of rabbits orally immunized with S. flexneri. Previously there have been very few studies concerning of regulation of antibody production in Shigella infections. These findings should increase our understanding of the cellular regulation of specific antibody responses to infections occurring at mucosal surfaces.