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.
D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D006912:Hydroxyquinolines / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000502:physiology; D051379:Mice; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects*
D006912:Hydroxyquinolines; D007376:Interleukin-2; D003208:Concanavalin A; C045282:roquinimex