Eva-Lotta Larsson

Mechanism of action of the new immunomodulator LS2616 on T cell responses

Spleen cells from mice treated with LS2616 display a highly increased response to the polyclonal T cell lectin ConA. The total number of splenic T cells, and the relative ratios between L3T4+ and Lyt-2+ T cells were not altered by LS2616 treatment. By dissecting the overall ConA response it was found that the number of ConA-inducible, IL-2 reactive T cells was unaffected, while ConA-induced IL-2 production was enhanced after LS2616 treatment. Spleen cells from LS2616 treated mice, depleted of G10 adherent macrophages (M phi) and reconstituted with M phi from untreated mice displayed normal levels of ConA responses. M phi depleted spleen cells from untreated animals, cocultured with M phi enriched populations from LS2616 treated animals resulted in an increased ConA response. Furthermore, spleen cells from treated mice were found to be excellent stimulators for alloantigen-induced T cell responses; when used as responders in MLC, however, these cells were comparable to responders from non-treated animals. Taken together the results demonstrate that LS2616 exerts an immunostimulatory effect on M phi, which indirectly facilitates polyclonal and antigen-specific T cell responses. The possible implications of this observation on various immunoregulatory events are discussed.

Interleukin-2 (IL-2) and its receptor.

The interleukin-2 (IL-2) receptor system which is responsible for T-cell cycle progression is a unique hormone-receptor system in that both the ligand and the receptor need to be induced. In the present article I will review the biological and molecular characteristics of IL-2 and its receptor, as well as the differential triggering and growth requirements that L3T4+(T4+) helper and Lyt-2+ (T8+) cytotoxic/suppressor T-cells display to respond. The various mechanisms of regulation operating to restrain clonal IL-2-dependent expansion of normal T-lymphocytes will be discussed.

Ionophore A23-187 induces responses to TCGF in mouse lymphocytes

The process of activation of T lymphocytes by ionophoric substances was analysed according to current concepts of T-lymphocyte activation. Proliferation induced by the ionophore A23-187 was found to be strictly dependent on the exogenous availability of growth factors. Lack of production of growth factors in spleen cell cultures containing the ionophore A23-187 explained the failure to directly stimulate mouse T-lymphocyte proliferation. It was concluded that the main action of A23-187 is the induction of expression of growth receptors, and that the increase in Ca++ uptake is, in itself, not sufficient to induce mitotic events.