TREATMENT OF CANDIDA-ALBICANS MANNAN-SPECIFIC DOWNREGULATORY CELL-POPULATIONS WITH DIVERGENT CONCENTRATIONS OF MONOPHOSPHORYL LIPID-A AND INTACT LIPOPOLYSACCHARIDE IN-VITRO ABROGATES THEIR EFFECT ON DELAYED-HYPERSENSITIVITY

We have shown previously that splenocytes from mice injected with Cand ida albicans mannan (MAN) suppress MAN-specific delayed hypersensitivi ty (DH) when transferred to immunized recipients and that treatment of donor mice with monophosphoryl lipid A (MLA) derived from Salmonella typhimurium or Salmonella minnesota shortly before transfer abrogated the downregulatory activity. me now show that treatment of splenocytes in vitro at 4 degrees C with 5 ng/ml MLA or 0.05 ng/ml S. typhimurium lipopolysaccharide (LPS) for 30 min before transfer also abrogated do wnregulatory activity. Higher or lower doses of MLA, 5 mu g or 5 pg, a ppeared to increase the suppressor activity slightly (5 mu g) or had n o effect (5 pg). LPS induced similar effects but the concentrations of LPS required to show the effects were 100-fold less than those of MLA . The effect of MLA appeared to be on cents) in the transfer populatio n involved in MAN-specific DH, in that spleen cells from normal mice t reated with MLA prior to transfer had no effect on DH. Finally, the po pulation of MLA-responsive cells mediating downregulation could not be concentrated on MLA-coated plates, suggesting that the MAN-specific d ownregulatory cell(s) either did not bind to MLA or did not bind to ML A with sufficient avidity to remain attached during the washing proced ures, The feasibility of abrogating suppression by treatment of lympho id cells in vitro will allow a more detailed analysis of the mechanism Of abrogation. (C) 1996 Academic Press,Inc.