Abstract
We previously showed that CD8+ T cells are required for optimal primary immunity to low dose Leishmania major infection. However, it is not known whether immunity induced by low dose infection is durable and whether CD8+ T cells contribute to secondary immunity following recovery from low dose infection. Here, we compared primary and secondary immunity to low and high dose L. major infections and assessed the influence of infectious dose on the quality and magnitude of secondary anti-Leishmania immunity. In addition, we investigated the contribution of CD8+ T cells in secondary anti-Leishmania immunity following recovery from low and high dose infections. We found that the early immune response to low and high dose infections were strikingly different: while low dose infection preferentially induced proliferation and effector cytokine production by CD8+ T cells, high dose infection predominantly induced proliferation and cytokine production by CD4+ T cells. This differential activation of CD4+ and CD8+ T cells by high and low dose infections respectively, was imprinted during in vitro and in vivo recall responses in healed mice. Both low and high dose-infected mice displayed strong infection-induced immunity and were protected against secondary L. major challenge. While depletion of CD4+ cells in mice that healed low and high dose infections abolished resistance to secondary challenge, depletion of CD8+ cells had no effect. Collectively, our results show that although CD8+ T cells are preferentially activated and may contribute to optimal primary anti-Leishmania immunity following low dose infection, they are completely dispensable during secondary immunity.
Highlights
The spectrum of disease collectively known as leishmaniasis continues to be a major threat to global health in many regions of the world
Beyond 3 weeks, there was no significant difference in the number of cells in the Draining lymph-node (dLN), despite continued difference in lesion size that lasted up to 8 weeks post-infection (Fig. 1A)
Clinical observations and experimental studies suggest that the development of effective cell-mediated immunity is essential for protection against leishmaniasis
Summary
The spectrum of disease collectively known as leishmaniasis continues to be a major threat to global health in many regions of the world. There is currently no effective licensed vaccine for prevention of human leishmaniasis. This is in part related to lack of proper understanding of the immunobiology of the disease, the factors that regulate the induction, maintenance and loss of protective immunity. It is widely believed that CD4+ T cells are the key lymphocyte subset that regulates anti-Leishmania immunity, studies utilizing low dose infections show that CD8+ T cells are important for optimal primary immunity [3,4]. No study has addressed the impact of parasite dose on the magnitude of initial T cell (both CD4+ and CD8+) expansion, and whether this affects the development of secondary anti-Leishmania immunity. The contribution of CD8+ T cells to low dose infection-induced resistance is not known
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