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Blood, 15 April 2004, Vol. 103, No. 8, pp. 3084-3092.
Prepublished online as a Blood First Edition Paper on December 24, 2003; DOI 10.1182/blood-2003-08-2867.

Submitted August 21, 2003
Accepted December 3, 2003
Uninfected erythrocytes inhibit P.falciparum-induced cellular immune responses in whole blood assays
Siske S Struik, Fakhreldin M Omer, Katerina Artavanis-Tsakonas, and Eleanor M Riley*
Department of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
* Corresponding author; email: eleanor.riley{at}lshtm.ac.uk.
Whole blood assays (WBA) have been successfully used as a simple tool for immuno-epidemiological field studies evaluating cellular immune responses to mycobacterial and viral antigens. Rather unexpectedly, we found very poor cytokine responses to malaria antigens in WBA in two immunoepidemiological studies carried out in malaria endemic populations in Africa. We have therefore conducted a detailed comparison of cellular immune responses to live (intact) and lysed malaria-infected erythrocytes in WBA and in peripheral blood mononuclear cell (PBMC) cultures. We observed profound inhibition of both proliferative and IFN- responses to malarial antigens in WBA as compared with PBMC cultures. This inhibition was seen only for malaria antigens (not mitogens or unrelated antigens), was independent of previous malaria exposure and blood group, and could not be overcome by increasing either antigen concentration or responder cell numbers. Inhibition was mediated by intact erythrocytes and occurred early in the culture period suggesting that failure of antigen uptake might underlie the lack of T cell responses. In support of this hypothesis, we have shown that intact uninfected erythrocytes specifically inhibit phagocytosis of infected red blood cells by peripheral blood monocytes. We propose that specific biochemical interactions with uninfected erythrocytes inhibit the phagocytosis of malaria infected erythrocytes and that this may impede T cell recognition in vivo.

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