CD8+ T cells are preferentially activated during primary low dose leishmania major infection but are completely dispensable during secondary anti-Leishmania immunity

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.
Author Summary It is known that CD8+ T cells are important for primary immunity to low dose L. major infection, but whether low dose-induced immunity is long lasting and whether CD8+ T cells are also important for memory immune response to low dose L. major is unknown. We studied whether infectious dose affects primary anti-Leishmania immunity and the contribution of CD8+ T cells in immunity following recovery from low and high dose infections. We found that low and high dose infections preferentially induced proliferation and cytokine production by CD8+ and CD4+ T cells, respectively, during early and late stages of infections. Also, both low and high dose-infected mice were solidly protected against secondary L. major challenge. Depletion of CD4+ cells in mice that healed low and high dose infections abolished resistance to secondary challenge, but depletion of CD8+ cells had no effect. Together, our results show that although CD8+ T cells are selectively activated and contribute to optimal primary immunity after low dose infection, they are not required for secondary immunity. This research further enhances our understanding of the immunobiology of cutaneous leishmaniasis.