T-CELL CONTROL OF IMMUNITY TO THE ASEXUAL BLOOD STAGES OF THE MALARIAPARASITE

Both antibody-dependent and antibody-independent mechanisms are involv ed in immune protection against the asexual blood stages of the malari a parasite. It is well established that T cells play a crucial role in both induction and maintenance of this immunity. Of the two T-cell su bsets (CD4(+), CD8(+)) carrying cdp T-cell receptors, the CD4(+) T cel ls are of major importance for the development of blood stage immunity in both experimental and human malaria. In mice, CD4(+) T cells compr ise at least two functionally distinct cell types (TH1, TH2), distingu ished on the basis of their lymphokine production. The balance between these subsets is critical for the outcome of an infection. In some ro dent malarias, TH1 cells producing IFN-gamma, and IL-2 are important f or controlling infection in its early phases, while TH2 cells, produci ng i.a. IL-4 and IL-IO, together with antibodies, are important for pa rasite clearance in later phases of infection. Distinct CD4(+) T cells of either TH1 or TH2 type also have regulatory functions in human P. falciparum infection. In contrast to the CD4(+) T cells, the role of C D8(+) T cells in blood stage infection appears to be limited, but supp ression of some CD4(+) activities has been reported for both experimen tal and human malaria. As in other infections, peripheral T cells equi pped with gamma/delta receptors are strongly upregulated in malaria an d also respond to parasite antigens in vitro by proliferation and lymp hokine production. However, the importance of the gamma/delta T cells for protection when compared with pathogenesis is presently unclear. R apid advances made in recent years in the characterization and cloning of plasmodial antigens eliciting immune protection have made it possi ble to define some of the antigenic structures involved in T-cell immu nity. This, together with an improved understanding of cellular mechan isms, provides some basis for the development of modern malaria vaccin es.