Experimental Human Plasmodium Falciparum Infections: Longitudinal Analysis of Lymphocyte Responses with Particular Reference to γδ T Cells

Abstract

The kinetics of the γδ T‐cell response was analysed in the context of the overall haematological response in subjects experimentally infected with sporozoites of Plasmodium falciparum. Numbers of γδ and αβ T cells and NK cells declined markedly during infection to reach minimum values 12–13 days post‐infection when the patients were ill. This decline commenced from the beginning of the erythrocytic cycle and well before parasites could be detected microscopically and clinical symptoms developed. Platelet numbers also declined. In vivo activation of γδ T cells was evident with sequential up‐regulation of the activation markers CD69 and HLA‐DR. γδ T cell numbers were highest after treatment with the majority being CD4⁻CD8⁻, HLA‐DR⁺ and showing reduced CD45RA expression. Contrary to some published observations γδ T‐cell percentages remained within the normal range. Little evidence of up‐regulation of activation or memory markers was observed in the αβ T‐cell population. In vitro proliferative responses to malaria antigen which involve γδ T cells were lost as the infection progressed and the lymphocyte count declined but these could be restored with the addition of exogenous IL‐2 to cultures. The authors findings are consistent with a protective and/or immunomodulatory role for γδ T cells in malaria.