Murine lymph node-derived stromal cells effectively support survival but induce no activation/proliferation of peripheral resting T cells in vitro

Abstract

Little is known about the homeostatic mechanisms by which the levels of peripheral lymphocytes are maintained. The survival of naïve T cells in vivo must be maintained by some factors that have not been characterized in an in vitro culture system. In this study, we established a culture system of stromal cells derived from murine lymph nodes and investigated the action of the stromal cells in supporting the survival of resting T cells in vitro. Most of the T cells cocultured with the stromal cells did not die, and the supernatant of cultured stromal cells increase the viability of T cells. This T-cell survival-supporting activity was maintained for more than 7 days. Although interleukin (IL)-4, IL-6, IL-7, and interferon-β also rescued peripheral T cells from spontaneous cell death, medium-soluble and heat-sensitive factor(s) derived from the stromal cells supported the survival of T cells more effectively and for a longer time than did these cytokines. T cells maintained in the culture system with the stromal cells appeared to remain in a resting G0/G1 state and did not show remarkable DNA synthesis. From these results, it is presumed that some soluble factor(s) other than the tested cytokines that have been identified as supporting T-cell survival are produced from lymph node stromal cells. These factor(s) play an important role in maintenance of resting T cells.