Use of recombinant interleukin-2 to enhance adoptive transfer of resistance to Listeria monocytogenes infection

Abstract

In vitro incubation of Listeria-immune spleen cells (LISC) with recombinant interleukin-2 (rIL-2) for at least 3 days increased their ability to transfer antilisteria resistance to recipient mice. This effect was blocked by the in vitro addition of transforming growth factor beta 1. The level of protection afforded by the transfer of rIL-2-incubated LISC was further elevated by the in vivo administration of rIL-2 at a dose that by itself did not significantly increase antilisteria resistance. The antilisteria resistance of recipient mice remained elevated for approximately 7 days and then rapidly declined to undetectable levels by 10 days. After cell transfer, recipient mice were protected against challenge with Listeria monocytogenes but not Salmonella typhimurium, Yersinia enterocolitica, or Streptococcus pyogenes. Flow cytometric analyses revealed an increase in the percentages of CD8+, NK+, and gamma delta T cell receptor+ cells but no change in the percentage of CD4+ cells as a result of LISC coculturing with rIL-2. In vitro depletion of CD4+ cells just prior to transfer had no significant effect on the adoptive transfer of resistance; depletion of CD8+ cells reduced the level of resistance by approximately 25%. Combined depletion of Thy-1.2+, CD4+, and CD8+ cells just prior to adoptive transfer diminished the level of protection in the spleens but not the livers of recipient mice. These data suggest that rIL-2 can be used to augment adoptive immunotherapy for bacterial infection in a manner similar to adoptive immunotherapy of human cancer patients. Although the protective cell population was not definitively identified, it appeared to be independent of CD4+ cells and only partly dependent on CD8+ cells.