Inhibition of Plasmodium falciparum growth in vitro by CD4+and CD8+T cells from non-exposed donors

Abstract

T cells from most adult non-exposed donors, which express a memory phenotype (CD45RO+), can respond by proliferation to P. falciparum asexual stages in vitro. Such cells may have arisen from exposure to environmental organisms. To address the efficacy of such cells in eliminating parasites and investigate the mechanisms involved, we have used an in vitro assay where parasite growth can be precisely monitored in the presence of different cell preparations. Unfractionated peripheral blood mononuclear cells (PBMC) from both malaria-exposed and non-exposed donors inhibited parasite growth by up to 62% in a two day assay. Purified T cells in the presence of adherent cells had a similar effect, but purified T cells alone or adherent cells alone had minimal effect. Antigens released at the time of schizont rupture were maximally effective in stimulating interferon-gamma (IFN gamma) production. Neutralizing antibodies to IFN gamma showed a partial reduction of growth inhibition in some individuals tested suggesting that different mechanisms may be operative. Neutralizing antibody to TNF alpha had a partial effect in combination with anti-IFN gamma. Antibodies to IL-1 and IL-4 had no effect. T cell fractionation experiments showed that while purified CD4+ T cells from some donors produced IFN gamma and inhibited parasite growth, purified CD8+ T cells could inhibit parasite growth to a greater extent without production of detectable IFN gamma.(ABSTRACT TRUNCATED AT 250 WORDS)