Regulation of the Immune Response in Plasmodium Falciparum Malaria. III. Proliferative Response to Antigen in Vitro and Subset Composition of T Cells from Patients with Acute Infection or from Immune Donors

T cells from patients with acute Plasmodium falciparum malaria were investigated for their proliferative responses in vitro to malarial antigen. Of 26 patients, 14 had acute and short lived (less than or equal to 8 days) disease episodes, most of them for the first time, while 12 had been ill for more than 8 days at the time of the blood samples were taken. The lymphocytes from the first group gave a weak, and apparently P. falciparum specific proliferation, peaking after 3-4 days, but waning within 5-6 days, suggesting the induction of suppression. No such responses were obtained with control antigen consisting of normal RBC membranes. The P. falciparum antigen-induced proliferative response was completely lacking in the second group of patients. Since both groups responded equally to T cell mitogen, the results are indicative of a malaria specific non-responsiveness. In contrast T cells from a group of apparently immune donors living in highly endemic P. falciparum malaria areas developed strong and long lasting proliferative responses to P. falciparum antigen with a peak on days 5-6. T cells from acutely infected P. vivax patients did not respond to either the P. falciparum antigen or to the control antigen. The cellular basis of the proliferative responses were investigated by surface marker studies with monoclonal antibodies. Within the T cell preparations, the T4+/T8+ cell ratio was close to normal for both the immune donors and for those with acute P. vivax infection. In contrast, this ratio was depressed for both groups of patients with acute P. falciparum infection. However, this was due to reduced number of circulating T4+ cells in the patients with short disease episodes whereas it was due to increased numbers of T8+ cells, probably including suppressor cells, in those who were ill for more than 8 days.