Regulation of human polymorphonuclear neutrophil (PMN) activity against Candida albicans by large granular lymphocytes via release of a PMN-activating factor.
Using a 24-hr radiolabel microassay developed in our laboratory that measures [3H]glucose uptake in residual Candida, we have identified the effector cells responsible for in vitro inhibition of Candida albicans growth as mainly polymorphonuclear neutrophils (PMN) and monocytes within the human peripheral blood cells. Highly purified T cells and large granular lymphocytes (LGL) that mediate natural killer activity which were obtained by Percoll density gradient centrifugation were found to have no innate activity against C. albicans. The LGL could not be activated by interferon-alpha, interferon-gamma or interleukin 2 to inhibit Candida growth although their K562 tumor cytotoxic activity was readily enhanced by these cytokines. Stimulation with heat-killed C. albicans also did not activate fungal growth inhibitory function in LGL and the supernatant of these activated LGL had no direct fungicidal activity. However, the activated LGL supernatant had the capability to enhance PMN function against C. albicans growth. Addition of recombinant human tumor necrosis factor, affinity-purified interferon-alpha, or interferon-gamma to PMN caused increased antifungal activity in PMN. However, antibodies to these cytokines had only a partial adverse effect on the ability of the activated LGL supernatant to stimulate PMN anti-Candida function. Therefore, the activated LGL supernatant appeared to contain a potent stimulator of PMN function which is as yet unidentified. These data indicate that LGL did not directly mediate anti-Candida activity but could indirectly influence C. albicans growth by activating PMN against the fungi through the release of a specific PMN-activating factor. Our findings therefore add another role to LGL which is the regulation of PMN function, the consequence of which is regulation of fungal immunity.
D002176:Candida albicans / Q000276:immunology*; D002469:Cell Separation; D004306:Dose-Response Relationship, Immunologic; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007158:Immunologic Techniques; D007372:Interferons / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008222:Lymphokines / Q000502:physiology*; D009504:Neutrophils / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007376:Interleukin-2; D008222:Lymphokines; D014409:Tumor Necrosis Factor-alpha; D007372:Interferons; D005947:Glucose