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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.

plos neglected tropical diseases

CD8+ T cells Are Preferentially Activated during Primary Low Dose Leishmania major Infection but Are Completely Dispensable during Secondary Anti-Leishmania Immunity