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CD8+ Granzyme B+–Mediated Tissue Injury vs. CD4+IFNγ+–Mediated Parasite Killing in Human Cutaneous Leishmaniasis
by
Barral, Aldina
, Ribeiro Cardoso, Cristina
, Tavares, Natalia
, de Oliveira, Camila I.
, Barral-Netto, Manoel
, Costa, Jackson
, Van Weyenbergh, Johan
, Brodskyn, Cláudia Ida
, Noronha, Almério
, Santos, Claire da Silva
, Boaventura, Viviane
, Lordelo, Morgana J.
, Borges, Valéria M.
in
Adolescent
/ Adult
/ Biomarkers - metabolism
/ CD4-Positive T-Lymphocytes - cytology
/ CD4-Positive T-Lymphocytes - immunology
/ CD4-Positive T-Lymphocytes - parasitology
/ CD8-Positive T-Lymphocytes - cytology
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - parasitology
/ Cell Movement - immunology
/ Cells, Cultured
/ Coculture Techniques
/ Female
/ Granzymes - immunology
/ Humans
/ In Situ Nick-End Labeling
/ Interferon-gamma - immunology
/ Leishmania braziliensis - immunology
/ Leishmaniasis, Cutaneous - immunology
/ Leishmaniasis, Cutaneous - pathology
/ Male
/ Middle Aged
/ Original
/ Skin - immunology
/ Skin - parasitology
/ Skin - pathology
/ T-Lymphocytes, Cytotoxic - cytology
/ T-Lymphocytes, Cytotoxic - immunology
/ T-Lymphocytes, Cytotoxic - parasitology
/ Young Adult
2013
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CD8+ Granzyme B+–Mediated Tissue Injury vs. CD4+IFNγ+–Mediated Parasite Killing in Human Cutaneous Leishmaniasis
by
Barral, Aldina
, Ribeiro Cardoso, Cristina
, Tavares, Natalia
, de Oliveira, Camila I.
, Barral-Netto, Manoel
, Costa, Jackson
, Van Weyenbergh, Johan
, Brodskyn, Cláudia Ida
, Noronha, Almério
, Santos, Claire da Silva
, Boaventura, Viviane
, Lordelo, Morgana J.
, Borges, Valéria M.
in
Adolescent
/ Adult
/ Biomarkers - metabolism
/ CD4-Positive T-Lymphocytes - cytology
/ CD4-Positive T-Lymphocytes - immunology
/ CD4-Positive T-Lymphocytes - parasitology
/ CD8-Positive T-Lymphocytes - cytology
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - parasitology
/ Cell Movement - immunology
/ Cells, Cultured
/ Coculture Techniques
/ Female
/ Granzymes - immunology
/ Humans
/ In Situ Nick-End Labeling
/ Interferon-gamma - immunology
/ Leishmania braziliensis - immunology
/ Leishmaniasis, Cutaneous - immunology
/ Leishmaniasis, Cutaneous - pathology
/ Male
/ Middle Aged
/ Original
/ Skin - immunology
/ Skin - parasitology
/ Skin - pathology
/ T-Lymphocytes, Cytotoxic - cytology
/ T-Lymphocytes, Cytotoxic - immunology
/ T-Lymphocytes, Cytotoxic - parasitology
/ Young Adult
2013
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CD8+ Granzyme B+–Mediated Tissue Injury vs. CD4+IFNγ+–Mediated Parasite Killing in Human Cutaneous Leishmaniasis
by
Barral, Aldina
, Ribeiro Cardoso, Cristina
, Tavares, Natalia
, de Oliveira, Camila I.
, Barral-Netto, Manoel
, Costa, Jackson
, Van Weyenbergh, Johan
, Brodskyn, Cláudia Ida
, Noronha, Almério
, Santos, Claire da Silva
, Boaventura, Viviane
, Lordelo, Morgana J.
, Borges, Valéria M.
in
Adolescent
/ Adult
/ Biomarkers - metabolism
/ CD4-Positive T-Lymphocytes - cytology
/ CD4-Positive T-Lymphocytes - immunology
/ CD4-Positive T-Lymphocytes - parasitology
/ CD8-Positive T-Lymphocytes - cytology
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - parasitology
/ Cell Movement - immunology
/ Cells, Cultured
/ Coculture Techniques
/ Female
/ Granzymes - immunology
/ Humans
/ In Situ Nick-End Labeling
/ Interferon-gamma - immunology
/ Leishmania braziliensis - immunology
/ Leishmaniasis, Cutaneous - immunology
/ Leishmaniasis, Cutaneous - pathology
/ Male
/ Middle Aged
/ Original
/ Skin - immunology
/ Skin - parasitology
/ Skin - pathology
/ T-Lymphocytes, Cytotoxic - cytology
/ T-Lymphocytes, Cytotoxic - immunology
/ T-Lymphocytes, Cytotoxic - parasitology
/ Young Adult
2013
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CD8+ Granzyme B+–Mediated Tissue Injury vs. CD4+IFNγ+–Mediated Parasite Killing in Human Cutaneous Leishmaniasis
Journal Article
CD8+ Granzyme B+–Mediated Tissue Injury vs. CD4+IFNγ+–Mediated Parasite Killing in Human Cutaneous Leishmaniasis
2013
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Overview
A protective or deleterious role of CD8+T cells in human cutaneous leishmaniasis (CL) has been debated. The present report explores the participation of CD8+T cells in disease pathogenesis as well as in parasite killing. CD8+T cells accumulated in CL lesions as suggested by a higher frequency of CD8+CD45RO+T cells and CD8+CLA+T cells compared with peripheral blood mononuclear cells. Upon Leishmania braziliensis restimulation, most of the CD8+T cells from the lesion expressed cytolytic markers, CD107a and granzyme B. Granzyme B expression in CL lesions positively correlated with lesion size and percentage of TUNEL-positive cells. We also observed a significantly higher percentage of TUNEL-positive cells and granzyme B expression in the biopsies of patients showing a more intense necrotic process. Furthermore, coculture of infected macrophages and CD8+T lymphocytes resulted in the release of granzyme B, and the use of granzyme B inhibitor, as well as z-VAD, Fas:Fc, or anti-IFN-γ, had no effect upon parasite killing. However, coculture of infected macrophages with CD4+T cells strongly increased parasite killing, which was completely reversed by anti-IFN-γ. Our results reveal a dichotomy in human CL: CD8+ granzyme B+T cells mediate tissue injury, whereas CD4+IFN-γ+T cells mediate parasite killing.
Publisher
Elsevier Inc,Nature Publishing Group
Subject
/ Adult
/ CD4-Positive T-Lymphocytes - cytology
/ CD4-Positive T-Lymphocytes - immunology
/ CD4-Positive T-Lymphocytes - parasitology
/ CD8-Positive T-Lymphocytes - cytology
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - parasitology
/ Female
/ Humans
/ Interferon-gamma - immunology
/ Leishmania braziliensis - immunology
/ Leishmaniasis, Cutaneous - immunology
/ Leishmaniasis, Cutaneous - pathology
/ Male
/ Original
/ T-Lymphocytes, Cytotoxic - cytology
/ T-Lymphocytes, Cytotoxic - immunology
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