Zaidi and coworkers (1) provide very convincing data indicating that γδ T cells are required for the generation of immunity induced by vaccination with irradiated Plasmodium berghei sporozoites. The mechanism of protection provided by this vaccination is not completely understood but is believed to be due to the induction of neutralizing anti-sporozoite Abs and CD8+ αβ T cell responses directed against parasites developing within the liver (2, 3). In combination, these immune responses interfere with the parasite life cycle by preventing development of the blood-stage parasites that cause morbidity and mortality associated with malaria.
The authors demonstrate increased frequencies of activated CD8+ T cells in blood, liver, and spleen after irradiated P. berghei sporozoite inoculation of wild-type but not γδ T cell–deficient mice. Protection from blood-stage parasitemia was not abrogated by γδ T cell depletion after irradiated sporozoite inoculation, suggesting that γδ T cells were not an immune effector but rather were required for induction of CD8+ T cell responses. However, Tsuji and coworkers (4) demonstrated that αβ T cell–deficient mice inoculated with irradiated Plasmodium yoelii sporozoites, through mosquito bites, inhibited the liver-stage parasites by >90% after sporozoite challenge and that this protection was abrogated if γδ T cells were depleted after vaccination. These data suggested a role for γδ T cells as an effector T cell. In addition, McKenna and coworkers (5) showed comparable inhibition of the liver-stage parasites after P. yoelii sporozoite challenge of irradiated sporozoite–vaccinated wild-type and γδ T cell–deficient mice. These data suggested that γδ T cells were not required for induction of αβ T cell responses directed against the liver-stage parasites.
What might account for the contrasting findings of these studies from three excellent laboratories? Differences in the immune responses to the distinct rodent malaria parasites (i.e., P. berghei and P. yoelii) is one clear possibility. Another possibility is that the quantity and the purity of sporozoites isolated by homogenization of mosquito salivary glands could affect the outcomes of the studies. A third possibility is that the administration of depleting Abs against γδ T cells after vaccination failed to eliminate CD8+ γδ TCR-low cells, which could represent a critical effector that eliminates the liver-stage parasites and/or the first merozoites released from liver schizonts that may share Ags with sporozoites.
We welcome a discussion on this subject.
- Copyright © 2018 by The American Association of Immunologists, Inc.
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