Abstract

Protective immunity against Plasmodium induced by immunization with irradiated sporozoites (SPZ) depends on both humoral and cellular responses. Although circumsporozoite protein (CSP)-specific cytolytic T lymphocyte responses have been established as an effector system, other cell 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 between 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 lymphokine production were tested in BALB/c, C57Bl/6, and C3H/HeN mice immunized according to different SPZ regimens. The levels of IL-2 paralleled the proliferative reactivities in each mouse strain examined. Although IFN gamma levels were present in the unprimed lymphocyte cultures, they increased following each SPZ immunization, in C57Bl/6, moderate in C3H/HeN, and lowest in BALB/c splenic cultures. Surprisingly, no IL-4 was detected in splenic cultures from any mouse strain during proliferative activity or protective immunity. In contrast, elevated IL-6 production was noted after each immunization, regardless of the protective 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 IL-4 secreting T cells were not induced by the SPZ-stage berghei antigens.

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