CELLULAR MECHANISMS IN THE IMMUNE-RESPONSE TO MALARIA IN PLASMODIUM VINCKEI-INFECTED MICE

Infection of mice with the malaria parasite Plasmodium vinckei vinckei is 100% lethal. However, after two infections followed by drug cure, BALB/c mice develop a solid immunity which is antibody independent but mediated by CD4(+) T cells. To elucidate the mechanisms of this immun ity, spleen cells from immune mice were challenged in vitro with lysat es of P. vinckei-infected or uninfected erythrocytes. The parasite ant igen induced proliferation of T cells from immune mice but not from no nimmune mice. When gamma interferon production by cells from immune mi ce was assayed at the single-cell level, 1 to 3 cells per 1,000 cells were found to release this cytokine when exposed to antigen. In contra st, the numbers of interleukin 4 (IL-4)-producing cells from both immu ne and control mice were less than or equal to 4 per 10(6) cells, rega rdless of antigen exposure. Investigation in a bioassay showed that P. vinckei antigen induced the release of IL-4 from spleen cells of immu ne mice but not from those of control mice. Nevertheless, that IL-4 is of minor significance in this system is also suggested by the absence of elevation of immunoglobulin E levels in blood samples from these m ice, in contrast to what is seen with P. chabaudi infection, in which IL-4-producing Th2 cells are of major importance for immunity during l ater phases of infection. Taken together, the present results indicate that immunity to P. vinckei is a Th1 response, with gamma interferon being an important protective factor. Whether or not the Th1 response, through overproduction of tumor necrosis factor alpha, is also respon sible for pathology and death in this infection remains to be clarifie d.