Induction and abrogation of LACK reactive cells in the evolution of human leishmaniasis.
Peripheral blood mononuclear cells (PBMC) from cutaneous leishmaniasis patients with ongoing Leishmania aethiopica infection and individuals cured/under treatment from L. infantum or L. donovani infection were stimulated in vitro with LACK, the Leishmania homologue of receptors for activated C kinase. The LACK protein is conserved in related leishmanial species and is expressed both in the promastigote and amastigote stages of Leishmania. Our results show that LACK induced marked NK and some CD8+ cell proliferation in PBMC from cutaneous leishmaniasis patients with active disease. These responses were coupled with high levels of IFN-gamma and IL-10 production. At the concentration tested, the proliferative responses to freeze-thawed Leishmania antigen (Ft-Leish) were higher, while the levels of IFN-gamma were consistently lower than that of LACK. Although cells from individuals cured of leishmaniasis could respond to whole Leishmania lysate by proliferation and IFN-gamma production, there was no evident response to LACK. Ethiopian controls tested at the same time also showed LACK induced proliferation with IFN-gamma and IL-10 responses. Thus LACK reactivity in terms of proliferation and cytokine induction were present in cells from some healthy donors and most of the patients with active lesions, while this response was absent in individuals cured of L. infantum or L. donovani leishmaniasis. Since cure from leishmaniasis often results in life-long protection, and active but not cured patients showed in vitro responses to LACK stimulation, questions arose as to how this highly immunodominant molecule functions during human leishmanisasis. Some possible mechanisms are discussed.
Maasho
K
K
Microbiology and Tumour biology Centre, Karolinska Institutet and Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
Wolday
D
D
Edjigu
M
M
Söderström
K
K
Britton
S
S
Akuffo
H
H
D000953:Antigens, Protozoan; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018572:Disease-Free Survival; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008213:Lymphocyte Activation; D015800:Protozoan Proteins / Q000276:immunology*
D000953:Antigens, Protozoan; D015800:Protozoan Proteins; D016753:Interleukin-10; C093139:LACK antigen, Leishmania; D007371:Interferon-gamma