Induction and Persistence in Vivo of NK/LAK Activity by a Mannoprotein Component of Candida albicans Cell Wall

Abstract

In a previous study we demonstrated that NK/LAK effectors are quickly induced in the peritoneal cavity of CD2F1 mice by a booster dose with inactivated Candida albicans (CA) cells or by the purified cell wall mannoprotein (MP), for a long time after CA sensitization. In this study we investigated the immunologic nature and kinetics of early events of the booster phenomenon. Intraperitoneal inoculation or CA in CD2F1 mice, 30 days after pretreatment with five doses of CA (2 × 10 7 cells/mouse) over a 2-week period (CA-5d treatment), elicited a very rapid recruitment of asialo GM1 + cells, L3T4 + cells, and Ly 2 + cells. Asialo GM1 + cells and Ly 2 + cells reached a maximum number 12 hr after the booster dose, while L3T4 + cells reached the maximum after 24 hr. The number of L3T4 + cells was about twofold greater than Ly 2 + cells at all times tested. A similar kinetic pattern was found after MP booster. In C57BL/6 mice we confirmed that CA and MP boosters induced LGL which express a NK antigen, detected by 3A4 mAb, and the activation marker CD25. The peak of non-MHC-restricted PEC cytotoxicity, which was reached 24 hr after MP or CA booster, did not correspond to the time (12 hr) for maximum number increase of asialo GM1 + cells and 3A4 + cells. Two hours after CA or MP booster in PEC there was a rapid and strong increase of IL-2 mRNA expression, which persisted at a high level 24 hr after booster. In CA-5d-pretreated mice, a persistent NK/LAK-like activity in the peritoneal cavity can be maintained by boosters with MP administered every 3 days. Such treatment, which we performed up to 15 days after CA sensitization, rendered the mice more responsive to further MP boosters. Effects of CA were not restricted to the peritoneal compartment because (a) there was a rebound of splenic NK activity about 10 days after CA-5d treatment by ip route and (b) CA given by iv route significantly increased splenic NK activity up to 15-20 days after CA-5d treatment. Recombinant human interleukin 2 (rhIL-2), given ip to mice (1000 U/mouse) in combination with CA during CA-5d treatment and with MP in the booster, strongly increased the level of peritoneal NK/LAK activity and PEC cellularity. The results seem to suggest that the immune mechanisms of the booster phenomenon involve an afferent phase of long-term memory and an effector phase of very quick aspecific activation of non-MHC-restricted cytotoxic effectors due to specific antigen recognition.