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*
Malaria Program, Naval Medical Research Center, Bethesda, MD 20889; and
Pan American Health Organization, Regional Office of the World Health Organization, Washington, DC 20037
CD8+ T cells have been implicated as critical effector
cells in protection against preerythrocytic stage malaria, including
the potent protective immunity of mice and humans induced by
immunization with radiation-attenuated Plasmodium spp.
sporozoites. This immunity is directed against the
Plasmodium spp. parasite developing within the host
hepatocyte and for a number of years has been presumed to be mediated
directly by CD8+ CTL or indirectly by IFN-
released from
CD8+ T cells. In this paper, in BALB/c mice, we establish
that after immunization with irradiated sporozoites or DNA vaccines
parasite-specific CD8+ T cells trigger a novel mechanism of
adaptive immunity that is dependent on T cell- and non-T cell-derived
cytokines, in particular IFN- and IL-12, and requires NK cells but
not CD4+ T cells. The absolute requirement for
CD8+ T cells to initiate such an effector mechanism, and
the requirement for IL-12 and NK cells in such vaccine-induced
protective immunity, are unique and underscore the complexity of the
immune responses that protect against malaria and other intracellular
pathogens.
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R. Wang, J. Epstein, F. M. Baraceros, E. J. Gorak, Y. Charoenvit, D. J. Carucci, R. C. Hedstrom, N. Rahardjo, T. Gay, P. Hobart, et al. Induction of CD4+ T cell-dependent CD8+ type 1 responses in humans by a malaria DNA vaccine PNAS, September 11, 2001; 98(19): 10817 - 10822. [Abstract] [Full Text] [PDF]
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