CD8+ T cells in cutaneous leishmaniasis: the good, the bad, and the ugly

Abstract

CD8(+) T lymphocytes are components of the adaptive immune response and play an important role in protection against many viral and bacterial infections. However, their role in parasitic infections is less well understood. In leishmaniasis, a disease caused by intracellular protozoan parasites of the genus Leishmania, CD8(+) T cells have been shown to be protective. However, increasing evidence indicates that CD8(+) T cells may also exacerbate disease. In this review, we will describe the situations where CD8(+) T cells are either good or bad for the outcome of the infection and attempt to reconcile the dual role played by CD8(+) T cells in cutaneous leishmaniasis.

Figure 1. Protective CD8⁺ T cells in leishmaniasis

CD8⁺ T cells producing IFN-γ activate macrophages, leading to parasite clearance. In addition, the IFN-γ produced by CD8⁺ T cells promotes increased production of IL-12, which amplifies the development of protective CD4⁺ Th1 cells. With low doses of parasites, CD8⁺ T cells are essential for blocking CD4 Th2 cells development.

Figure 2. Pathologic CD8⁺ T cells in leishmaniasis

Leishmania-specific CD8⁺ T cells migrate to leishmanial lesions and lyse infected cells, leading to the release of proinflammatory molecules, including molecules with damage-associated molecular patterns (DAMPS). Lysis of infected cells leads to release of parasites, which may promote increased metastasis of the parasites. Memory CD8⁺ T cells generated from prior non-leishmanial infections are also recruited to leishmanial lesions. Leishmania infection leads to upregulation of ligands for NKG2D, such as Rae1γ, and thus if the recruited CD8⁺ T cells express NKG2D they lyse target cells, also leading to cell death and increased inflammation.