Self-healing Cutaneous Leishmaniasis Research Articles

The Leishmania promastigote surface antigen-2 (PSA-2) is specifically recognised by Th1 cells in humans with naturally acquired immunity to L. major.

The promastigote surface antigen-2 (PSA-2) is a Leishmania parasite antigen, which can induce Th1-mediated protection against murine leishmaniasis when used as a vaccine. To evaluate PSA-2 as a human vaccine candidate the specific T-cell response to PSA-2 was characterised in individuals immune to cutaneous leishmaniasis. Peripheral blood mononuclear cells from Sudanese individuals with a past history of self-healing cutaneous leishmaniasis proliferated vigorously in response to PSA-2 isolated from Leishmania major, whereas the antigen did not activate cells from presumably unexposed Danes. Peripheral blood mononuclear cells from individuals with previous L. major infection had varying proliferative responses to PSA-2 derived from L. donovani promastigotes. Peripheral blood mononuclear cells activated by PSA-2 from L. major produced high amounts of interferon-gamma and tumour necrosis factor-beta, and little interleukin-4, thereby showing a Th1 cytokine pattern. Parallel cultures showed clear Th1 and Th2 response patterns to purified protein derivative of tuberculin or tetanus toxoid, respectively. Flow cytometric analysis revealed that PSA-2 induced blastogenesis in the CD3 positive population and that these cells were the major source of interferon-gamma. The results show that Th1-like cells recognising PSA-2 are expanded during infection by L. major and that they maintain their Th1-like cytokine profile upon reactivation in vitro. Since immunity to cutaneous leishmaniasis is mediated by antigen-specific Th1-like cells, PSA-2 might be considered a vaccine candidate for human leishmaniasis.

The Leishmania promastigote surface antigen-2 (PSA-2) is specifically recognised by Th1 cells in humans with naturally acquired immunity to L. major

The promastigote surface antigen-2 (PSA-2) is a Leishmania parasite antigen, which can induce Th1-mediated protection against murine leishmaniasis when used as a vaccine. To evaluate PSA-2 as a human vaccine candidate the specific T-cell response to PSA-2 was characterised in individuals immune to cutaneous leishmaniasis. Peripheral blood mononuclear cells from Sudanese individuals with a past history of self-healing cutaneous leishmaniasis proliferated vigorously in response to PSA-2 isolated from Leishmania major, whereas the antigen did not activate cells from presumably unexposed Danes. Peripheral blood mononuclear cells from individuals with previous L. major infection had varying proliferative responses to PSA-2 derived from L. donovani promastigotes. Peripheral blood mononuclear cells activated by PSA-2 from L. major produced high amounts of interferon-γ and tumour necrosis factor-β, and little interleukin-4, thereby showing a Th1 cytokine pattern. Parallel cultures showed clear Th1 and Th2 response patterns to purified protein derivative of tuberculin or tetanus toxoid, respectively. Flow cytometric analysis revealed that PSA-2 induced blastogenesis in the CD3 positive population and that these cells were the major source of interferon-γ. The results show that Th1-like cells recognising PSA-2 are expanded during infection by L. major and that they maintain their Th1-like cytokine profile upon reactivation in vitro. Since immunity to cutaneous leishmaniasis is mediated by antigen-specific Th1-like cells, PSA-2 might be considered a vaccine candidate for human leishmaniasis.

Characterization of the Immune Response in Subjects with Self-Healing Cutaneous Leishmaniasis

In patients with cutaneous leishmaniasis in areas of Leishmania braziliensis transmission, ulcers may heal without therapy. In the present study, we evaluated the T cell responses of 10 subjects who two years earlier had a rapidly (less than three months) self-healing cutaneous disease. The immunologic responses of these cases were determined by intradermal skin test, measurements of antibodies, lymphocyte proliferative responses, and interferon-gamma (IFN-gamma) production in cultures stimulated with Leishmania antigens. These data were compared with those observed in 10 other patients with active cutaneous and mucosal leishmaniasis. Evidence of strong lymphocyte blastogenesis and IFN-gamma production was observed in eight of 10 patients with self-healing cutaneous leishmaniasis, with stimulation indices ranging from 32 to 506, and IFN-gamma levels ranging from 500 to 2,900 pg/ml. The mean +/- SD stimulation index of the lymphocyte proliferative responses (288 +/- 247) and the mean +/- SD of IFN-gamma production after stimulation with Leishmania antigen (970 +/- 960 pg/ml) in subjects with self-healing cutaneous leishmaniasis were similar (P > 0.05) to those observed in patients with mucosal disease (stimulation index = 308 +/- 282 and IFN-gamma level = 838 +/- 819 pg/ml). These responses were higher (P < 0.01) than those observed in patients with active cutaneous leishmaniasis (stimulation index = 50 +/- 82 and IFN-gamma level = 264 +/- 336 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Th1-like human T-cell clones recognizing Leishmania gp63 inhibit Leishmania major in human macrophages.

The major surface protease of Leishmania major, gp63, has been suggested as a vaccine candidate for cutaneous leishmaniasis. In this study gp63 was purified from L. major promastigotes. A panel of human T-cell clones recognizing this protein were generated from individuals who had previously had self-healing cutaneous leishmaniasis. The T-cell clones expressed CD4, and the alpha chain of the T-cell antigen receptor. GP63 reactive T-cell clones activated by antigen or by immobilized anti-CD3 antibody released relative large amounts of interferon-gamma and no or little interleukin-4, thereby resembling Th1 cells. Autologous mononuclear cells and Epstein-Barr virus-transformed B cell lines were equally efficient in presenting the antigen to the T cells. The gp63 reactive T cells induced resistance to infection in cultured human macrophages by L. major. The data confirm that human CD4+ T cells recognizing gp63 can take part in the host defence against L. major infections.

Experimental cutaneous leishmaniasis: Langerhans cells internalize Leishmania major and induce an antigen-specific T-cell response.

Human leishmaniasis constitutes a diverse group of diseases caused by protozoa of the genus Leishmania. The parasites are transmitted by sandflies and the infection is initiated by introduction of promastigotes into the skin at the site of the vector’s bite. In the mammalian host, Leishmania parasites exist as obligatory intracellular amastigotes residing in mononuclear phagocytes. The diseases vary in severity from the self-healing cutaneous leishmaniasis, characterized by a localized cutaneous lesion at the site of primary infection, to the progressive visceral leishmaniasis, where the parasites disseminate from the original skin lesion to local lymph nodes and then to spleen, liver and bone marrow. The clinical manifestation depends primarily on the species of parasite, but also on the genetic make-up of the host. The T cell-mediated immunity is crucial for the outcome of infection because activated T cells release various lymphokines that promote either the spreading or the elimination of parasites1,2.KeywordsEpidermal CellCutaneous LeishmaniasisLeishmania ParasiteParasite AntigenMajor Antigen

Leishmania mexicana: Immunology and histopathology in C3H mice

C3H mice were infected subcutaneously with 10 5 promastigotes of Leishmania mexicana and subsequent lesions were examined at 3, 5, and 8 months. All animals developed persistent nonulcerating nodules of variable size which did not metastasize. The nodules contained amastigotes with a mononuclear infiltrate of histiocytes, lymphocytes, and plasma cells, but without formation of tuberculoid-type granulomas. Neutrophils and eosinophils were also encountered in some cases. Specific antileishmanial antibodies and delayed-type hypersensitivity to leishmanial antigen were present at 3, 5, and 8 months postinfection. L. mexicana infection in C3H mice differs from classic self-healing cutaneous leishmaniasis by the pesistence of nonhealing, nonulcerating, nonmetastasizing lesions, despite evidence of cellular and humoral immunity.