A new immunomodulator, LF 1695--II. Effects on allogenic and antigenic responses

LF 1695, a chemically defined immunomodulator has been shown to induce in vitro T-cell differentiation and to potentiate mitogenic proliferation. The effects of LF 1695 on antigenic and allogenic responses were studied in vitro and lymphocyte proliferation was estimated by 3H-thymidine uptake for 5 and 6 days, respectively. Human peripheral blood lymphocytes (PBL) from tuberculin sensitive donors were significantly stimulated by purified protein derivative (PPD) in the presence of LF 1695. Optimal lymphocyte proliferation with PPD was obtained at 0.5 micrograms/ml LF 1695. The ability of LF 1695 to enhance proliferation of PBL in an allogenic reaction was also examined. LF 1695 (0.2 micrograms/ml) enhanced the proliferation of PBL from two individuals with different HLA DR loci in the bilateral mixed lymphocyte reaction (MLR). Moreover, LF 1695 was tested in vivo in the experimental graft vs host reaction (GvHR) in mice. CBA, H2k mice receiving a lethal dose of irradiation were injected with spleen cells from LF 1695-treated or untreated C57 Bl/6, H2b mice via different routes. CBA mice were found to have a spleen weight x 1000/body ratio up to 1.5 when injected with cells from untreated C57 Bl/6 mice. Mice treated intraperitoneally with LF 1695 at 2.5 or 5 mg/kg/day showed an increase of GvHR intensity with splenic index of 1.71 and 1.80, respectively. When the animals were treated continuously through drinking water containing LF 1695 (4 mg/kg, 10 mg/kg or 100 mg/kg), these ratios were: 1.82, 1.10 and 1.37, respectively. Finally, LF 1695 enhanced GvHR significantly when used at low doses, while high doses induced a decrease of GvHR intensity.(ABSTRACT TRUNCATED AT 250 WORDS)