IMMUNIZATION WITH IRRADIATED PLASMODIUM-BERGHEI SPOROZOITES INDUCES IL-2 AND IFN-GAMMA BUT NOT IL-4

Protective immunity against Plasmodium induced by immunization with ir radiated sporozoites (SPZ) depends on both humoral and cellular respon ses. Although circumsporozoite protein (CSP)-specific cytolytic T lymp hocyte responses have been established as an effector system, other ce ll types are required for protection. We have previously demonstrated that although protective immunity and T cell proliferative reactivity to SPZ are mouse strain- and SPZ dose-dependent, no correlation betwee n the two responses could be found. Since protective immunity involves functionally diverse T cell subsets, we asked whether the discordance between proliferative responses to SPZ and protective immunity might have resulted from selective activation of either the Th1 or Th2 cell subset. Protective immunity, in vitro proliferative responses, and lym phokine production were tested in BALB/c, C57B1/6, and C3H/HeN mice im munized according to different SPZ regimens. The levels of IL-2 parall eled the proliferative reactivities in each mouse strain examined. Alt hough IFN gamma levels were present in the unprimed lymphocyte culture s, they increased following each SPZ immunization, in C57B1/6, moderat e in C3H/ HeN, and lowest in BALB/c splenic cultures. Surprisingly, no IL-4 was detected in splenic cultures from any mouse strain during pr oliferative activity or protective immunity. In contrast, elevated IL- 6 production was noted after each immunization, regardless of the prot ective status and it correlated with anti-CSP IgG serum levels. These data establish that lymphokine profiles corresponding primarily to the Th1 cells were induced by immunization with P. berghei SPZ and that I L-4 secreting T cells were not induced by the SPZ-stage berghei antige ns.