Identification of antigens recognized by T cells in human leishmaniasis: analysis of T-cell clones by immunoblotting

Melby, Peter C.; Sacks, David L.

doi:10.1128/iai.57.10.2971-2976.1989

Cited by 29 publications

(10 citation statements)

References 19 publications

(21 reference statements)

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“…These authors studied the responsiveness of these clones to individual antigens of Leishtnania, and noted ihai IFN-y production was associated with proliferation. The results [17] were interpreted by ihe authors as showing that following healing of past infection with Leishmania there was the development of clones of T cells that produce H N-y and lluit it is these cells thai would render the individual resistant to reinfection wilh Leishmania, In our system the lack of correlalion between the levels of IFN-y and the percent inhibition of amastigotes suggests ihaithere may be other factors required for the adequate killing of L. aethiopica. an infection that generally heals more slowly than /.. major.…”

Section: Discussionmentioning

confidence: 61%

“…In the murine model, control of exaeerbalion of eulaneous disease appears to be associated wilh a subset of CD4' T cells whieh produce IFN--; in response lo antigenic stimulation [6). In the human system Melby & Sacks [17] have deseribed CD4', lFN-y-producing T cell clones derived from individuals wilh past history of Leishmania infection. These authors studied the responsiveness of these clones to individual antigens of Leishtnania, and noted ihai IFN-y production was associated with proliferation.…”

Section: Discussionmentioning

confidence: 99%

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Contribution of non-Leishmania-specific immunity to resistance to Leishmania infection in humans

Akuffo

Britton

1992

Clinical and Experimental Immunology

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SUMMARYLymphocytes ofindivlduals from a country non-endemic for Leishmania (Sweden), responded wiih a vigorous interferon-gamma (IFN--/) and IL-6 response when exposed to live or dead promastigotcs of Leishmania aethiopica. This response was sometimes as strong as when the same cells were exposed lo the mitogen (phytohaetnaggluiinin (PMAl). Furthermore, supernatants of cells exposed to Leishmania promastigotcs were able to inhibit the amastigote form of the same parasite, ln some few instances there was no such reactivity to Leishmania parasites, [t is proposed that most individuals have such a first line cytokine response which is enough to prevent further spread and growth of lhe parasites. In exposed individuals who display disease symptoms, this non-Leishniania-specific response is overcome (by dose) or is weak (for genetic reasons). In the latter instances curbing of parasite growth would depend on acquired immunity.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Contribution of non-Leishmania-specific immunity to resistance to Leishmania infection in humans

Akuffo

Britton

1992

Clinical and Experimental Immunology

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“…Among the amastigote SLA subfractions, the first fraction resulted in a higher proliferative response and IFN-7 production by T cells in comparison with other fractions. The heterogeneity in the pattern of responses in recovered cases may have been contributed to by the extent and duration of infection or the genetic restriction of the host anti-leishmania1 T cells [41]. Overall, the proliferative response of T cells of non-healed patients was not as high as in recovered cases.…”

Section: Discussionmentioning

confidence: 90%

Biochemical analysis and immunogenicity ofLeishmania majoramastigote fractions in cutaneous leishmaniasis

Rafati

Couty-Jouve

Alimohammadian

et al. 1997

Clinical and Experimental Immunology

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SUMMARYSoluble Leishmania antigen (SLA) from both developmental stages of L. major (L. major MRHO/IR/75/ ER) were prepared. Three and five subfractions of SLA from amastigote and promastigote were obtained by fast protein liquid chromatography (FPLC), respectively. Biochemical analyses and comparison of amastigote and promastigote SLA were done. The biochemical analyses revealed that the first fraction of L. major amastigote possesses a distinct band on its electrophoretic mobility pattern corresponding to a position of 24kD, and it has enzymatic activity with characteristics of a cysteine proteinase. The isolated fractions of amastigote were tested for induction of proliferation, interferongamma (IFN-y) and IL-4 production in cultures of peripheral blood mononuclear cells (PBMC) from individuals who had recovered and also chronic patients of cutaneous leishmaniasis caused by L. major. The cells of recovered individuals compared with chronic cases proliferated profoundly in response to the first fraction of amastigote SLA. In all recovered individuals, the IFN-y, but not IL-4, was secreted in response to stimulation with the first fraction of amastigote SLA. In chronic cutaneous leishmaniasis, IFN-y was infrequently observed in response to stimulation by all three fractions of amastigote SLA, but secretion of IL-4 was observed. These data indicate that first fraction of amastigote SLA is a strong inducer of primed human immune response to L. major, and may have a protective function.

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“…Healing of cutaneous lesions is associated with ulcer formation. Following healing of a clinically apparent leishmaniasis infection, the development of gamma interferon (IFN-␥)-producing T-cell clones is believed to render the individual resistant to leishmaniasis (15).…”

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confidence: 99%

Indications of the Protective Role of Natural Killer Cells in Human Cutaneous Leishmaniasis in an Area of Endemicity

et al. 1998

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The role of natural versus acquired immunity to Leishmania aethiopica infection in humans is the focus of our studies. We found in previous studies that mononuclear cells from nonexposed healthy Swedish donors responded to Leishmania antigen stimulation by proliferation and gamma interferon production. The main cell type responding was CD3− CD16/56+ natural killer (NK) cells. These findings led us to suggest that the potential to produce a rapid, nonacquired NK cell response may be a protective phenotype. In order to test this hypothesis, an area in Ethiopia whereLeishmania is endemic was selected, and peripheral blood mononuclear cells were obtained from individuals who had lived in the area most of their lives but had no evidence of past or present leishmaniasis. Their responses were compared with those of confirmed leishmaniasis patients from the same region with active lesions or cured leishmaniasis lesions. Cells from these donors were stimulated in vitro with L. aethiopica antigen. Responses were measured by proliferation, cytokine production, and phenotype analysis by fluorescence-activated cell sorting. The association ofNRAMP1 alleles with the studied phenotype and susceptibility to L. aethiopica-induced leishmaniasis was also evaluated. The results show that Leishmania antigens can induce NK cell and CD8+-T-cell responses in vitro. This is clearly seen in proliferating cells from the cured (immune) individuals and the apparently protected controls from the area of endemicity. It contrasted with the reactivity of the patients, where some NK proliferation was coupled with enhanced CD4+-T-cell proliferation. We conclude from these observations that NK cells and CD8+ cells proliferating in response toLeishmania stimulation are involved in protection from and healing of (Ethiopian) cutaneous leishmaniasis; however, such mechanisms appear to be unrelated to the NRAMP1 host resistance gene.

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Identification of antigens recognized by T cells in human leishmaniasis: analysis of T-cell clones by immunoblotting

Cited by 29 publications

References 19 publications

Contribution of non-Leishmania-specific immunity to resistance to Leishmania infection in humans

Contribution of non-Leishmania-specific immunity to resistance to Leishmania infection in humans

Biochemical analysis and immunogenicity ofLeishmania majoramastigote fractions in cutaneous leishmaniasis

Indications of the Protective Role of Natural Killer Cells in Human Cutaneous Leishmaniasis in an Area of Endemicity

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