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.

Lymphocytic Choriomeningitis Virus Expands a Population of NKG2D+CD8+ T Cells That Exacerbates Disease in Mice Coinfected with Leishmania major

“…CD8 T cells are protective in leishmaniasis, both during a primary and secondary infection, and can also mediate protection in leishmanial vaccines (21). Paradoxically, however, it is now clear that CD8 T cells also induce increased pathology in cutaneous leishmaniasis (21–25).…”

“…Paradoxically, however, it is now clear that CD8 T cells also induce increased pathology in cutaneous leishmaniasis (21–25). We previously identified two types of pathologic CD8 T cells in mice, a population that are Leishmania- specific and another population of bystander memory CD8 T cells (7, 22).…”

“…CD8 T cells play a protective role in leishmaniasis, due to their production of IFN-γ that can both activate macrophages to kill the parasites and enhance the CD4+ Th1 response (21). However, there is increasing evidence that CD8 T cells also act to promote tissue damage in cutaneous leishmaniasis (22, 32).…”

Assessment of Protection Induced by DNA and Live Vaccine Encoding Leishmania MHC Class I Restricted Epitopes against L. major Challenge in Balb/c Mice Model

“…+ T-cells' contribution is undoubtedly necessary for VL control but remains controversial regarding CL control [15,16]. Our previous study clearly evaluated CD8 + T-cells stimulation by a polytope construct containing H-2Kd restricted epitopes from non-vaccine protein candidates of Leishmania major [17].…”

Memory T cells in cutaneous leishmaniasis

“…The recent identification of a protein, phosphoenolpyruvate carboxykinase, that reacts with approximately 20% of L. major -specific CD4 T cells and has broad cross-reactivity may help resolve this need, and will also be an invaluable tool for assessing CD4 responses [29]. CD8 T cells have been shown to be protective in some vaccine and mouse models [64], but also might be problematic as CD8 cytotoxic lymphocytes are associated with increased pathology in Leishmania braziliensis [23,65]. …”