Extrathymic T cells in malaria protection, including evidence for the onset of erythropoiesis in the liver during infection.

This review proposes the possibility that malarial protection might not be achieved through the process of acquired immunity in which the constituents are conventional T and B (B-2) cells. On the other hand, malarial protection might be achieved by the process of innate immunity in which the constituents are extrathymic T cells and autoantibody-producing B-1 cells. Accordingly, mice infected with malaria exhibited severe thymic atrophy, and the expansion of IL-2Rbeta+ CD3int cells and its subset of NK1.1-CD3int cells were simultaneously induced. In parallel with the expansion of extrathymic T cells in the liver, extramedullary erythropoiesis was found to begin in the liver of these mice. Interestingly, malarial protozoa were primarily seen in only these nucleated erythrocytes in the liver at the early stage of infection. These results suggest that malaria immunology falls into a new field of immunology, namely, innate immunity. The similarity of the immune states among malaria, aging, and autoimmune diseases also suggest that the immunosuppression of a conventional, acquired immune system is more likely the common mechanism underlying these diseases or physiological responses.