ALTERATIONS IN FREQUENCY OF INTERLEUKIN-2 (IL-2)-SECRETING, GAMMA INTERFERON-SECRETING, OR IL-4-SECRETING SPLENOCYTES INDUCED BY CANDIDA-ALBICANS MANNAN AND OR MONOPHOSPHORYL-LIPID-A/

We have shown previously that intravenous injection of Candida albican s mannan (MAN) into naive mice induced CD8(+) effector downregulatory cells and that such cells were not produced if mice were deficient in CD4(+) or I-A(+) cells during the early interval (less than or equal t o 30 h) following the introduction of MAN, Moreover, the nonspecific b iological response modifier monophosphoryl lipid A (MPL), given in viv o or incubated with cells in vitro, can abrogate the MAN-specific immu nomodulatory activity, The mechanism by which the abrogation is mediat ed is unknown, but it is hypothesized to involve cytokines, Therefore, we measured the number of cytokine-secreting cells for the Th1 cytoki ne interleukin-2 (IL-2) and the Th2 cytokine IL-4, as well as for gamm a interferon (IFN-gamma), in splenocyte populations from MAN and/or MP L-treated mice, using an enzyme-linked immunospot assay designed to de tect individual cytokine-secreting cells (spot-forming cells [SFC]), C ytokine-secreting cells were demonstrated in cell suspensions enriched for CD4(+) cells, but no SFC could be demonstrated in populations enr iched for CD8(+) cells, Both MAN and MPL, when administered to separat e groups of animals, stimulated the production of increased numbers of cytokine-producing cells for each of the three cytokines tested, The response with respect to IL-4-secreting cells, however, was the most s triking, Despite the fact that MAN and MPL independently caused increa ses in SFC to all three cytokines, when both MAN and MPL were administ ered to the same animal, all increases were reversed, and the numbers of SFC detected were at or below those detected in saline control anim als, These data support the hypothesis that IL-4 is involved in MAN-sp ecific immunoregulatory activities, The data also emphasize the fact t hat two immuno-modulators, i.e., MAN and MPL, having similar effects w hen given in vivo independently, may be antagonistic when administered sequentially to the same animal.