NAIVE HUMAN ALPHA-BETA T-CELLS RESPOND TO MEMBRANE-ASSOCIATED COMPONENTS OF MALARIA-INFECTED ERYTHROCYTES BY PROLIFERATION AND PRODUCTION OF INTERFERON-GAMMA

Crude extracts of Plasmodium falciparum schizont-infected erythrocytes (PfSE) induce polyclonal activation of peripheral blood T lymphocytes from naive (malaria unexposed) humans. We demonstrate that the active component of PfSE is membrane bound, soluble in sodium dodecyl sulpha te (SDS) and partially heat stable, but distinct from the tumour necro sis factor (TNF)-inducing, exoantigen-like activity of schizont extrac ts. Malaria pigment induces little or no T-cell activation. The respon ding cells are predominately CD4(+), CD45RO(+), T-cell receptor (TCR)a lpha beta(+). Contrary to previous reports, expansion of the TCR gamma delta(+) subset was observed in cells from only one of eight donors. Proliferating cells secrete interferon-gamma (IFN-gamma) and release l arge amounts of soluble interleukin-2R (sIL-2R) into the culture super natant but produce no detectable interleukin-4 (IL-4), a phenotype typ ical of the T-helper (Th)1 subset of CD4(+) T cells. We propose that t hese activated T cells may initiate the inflammatory response to malar ia infection in non-immunes and may contribute to the pathology of the disease.