EXPERIMENTAL HUMAN PLASMODIUM-FALCIPARUM INFECTIONS - LONGITUDINAL ANALYSIS OF LYMPHOCYTE-RESPONSES WITH PARTICULAR REFERENCE TO GAMMA-DELTA T-CELLS

The kinetics of the gamma delta T-cell response was analysed in the co ntext of the overall haematological response in subjects experimentall y infected with sporozoites of Plasmodium falciparum. Numbers of gamma delta and alpha beta T cells and NK cells declined markedly during in fection to reach minimum values 12-13 days postinfection when the pati ents were ill. This decline commenced from the beginning of the erythr ocytic cycle and well before parasites could be detected microscopical ly and clinical symptoms developed. Platelet numbers also declined. In vivo activation of gamma delta T cells was evident with sequential up -regulation of the activation markers CD69 and HLA-DR, gamma delta T c ell numbers were highest after treatment with the majority being CD4(- )CD8(-), HLA-DR(+) and showing reduced CD45RA expression. Contrary to some published observations gamma delta T-cell percentages remained wi thin the normal range. Little evidence of upregulation of activation o r memory markers was observed in the alpha beta T-cell population. In vitro proliferative responses to malaria antigen which involve gamma d elta T cells were lost as the infection progressed and the lymphocyte count declined but these could be restored with the addition of exogen ous IL-2 to cultures. The authors findings are consistent with a prote ctive and/or immunomodulatory role for gamma delta T cells in malaria.