MECHANISMS OF INHIBITION OF CRYPTOCOCCUS-NEOFORMANS BY HUMAN-LYMPHOCYTES

Recently, our laboratory and others have demonstrated that human perip heral blood T and NK lymphocytes directly inhibit the growth of Crypto coccus neoformans, In this study, we further define the conditions und er which lymphocyte-mediated fungistasis against C. neoformans occurs and examine whether mechanisms implicated in lymphocyte-mediated activ ities against other target cells are also involved in anticryptococcal activity, The addition of whole or broken heat-killed C. neoformans m odestly inhibited lymphocyte-mediated fungistasis, whereas other parti culates had no effect, The hydroxyl radical scavenger catechin, but no t diethyl urea or propyl gallate, profoundly inhibited fungistasis. Sa licylic acid inhibited fungistasis in a dose-dependent fashion, Howeve r, two other cyclooxygenase inhibitors, piroxicam and indomethacin, ha d no effect, suggesting that the mechanism of inhibition by salicylic acid was cyclooxygenase independent, Reagent prostaglandin E(2), at co ncentrations shown by others to inhibit NK cell-mediated bactericidal and tumorlytic activities, had no effect on lymphocyte-mediated fungis tasis, The addition of selected monoclonal antibodies or ligands react ive with receptors on human lymphocytes had no significant effect on l ymphocyte-mediated fungistasis, Acapsular, small-capsuled, and large-c apsuled C, neoformans organisms were inhibited by lymphocytes to an ap proximately equal extent, These data demonstrate that lymphocyte-media ted activity against C, neoformans proceeds regardless of the presence of capsule and by mechanisms at least in part dissimilar from those s een with other target cells.