DOES THE MECHANISM OF PROTECTION FROM FALCIPARUM-MALARIA BY RED-CELL GENETIC-DISORDERS INVOLVE A SWITCH TO A BALANCED T(H)1 T(H)2 CYTOKINE PRODUCTION MODE/

The mechanism of protection from falciparum malaria by red cell geneti c disorders still remains controversial. Decreased survival of parasit es in variant red cells has previously been proposed. However, in vitr o experiments were not conclusive and do not seem sufficient to explai n the substantial degree of in vivo protection afforded to red cell ge netic trait carriers. Evidence has recently been accumulating in favou r of enhancement of the host immune response by these genetic traits. Malaria-infected variant red cells undergo modifications to their anti genicity which lead to accelerated and selective removal of early bloo d-stage parasites by splenic macrophages, resulting in fewer parasites reaching schizogony. Consequently there will be alterations in antige n processing, presentation and recognition which could explain the dif ferences observed in T-cell responses between trait carriers and norma l individuals. It is suggested that exposure to a lower dose of early parasite-stage antigens rather than the exoantigens of late mature sch izonts could lead during primary and subsequent secondary infections t o differentiation of T-helper cells into balanced T(H)1/T(H)2 subsets that promote protection, reversing the susceptibility to the fatal com plications of falciparum malaria.