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A recombinant Leishmania antigen that stimulates human peripheral blood mononuclear cells to express a Th1-type cytokine profile and to produce interleukin 12.

ABSTRACT: Leishmania braziliensis causes cutaneous and mucosal leishmaniasis in humans. Most patients with cutaneous leishmaniasis heal spontaneously and may therefore have developed protective immunity. There appears to be a mixed cytokine profile associated with active cutaneous or mucosal disease, and a dominant T helper (Th)1-type response associated with healing. Leishmanial antigens that elicit these potent proliferative and cytokine responses from peripheral blood mononuclear cells (PBMC) are now being identified. Herein, we report on the cloning and expression of a L. braziliensis gene homologous to the eukaryotic ribosomal protein eIF4A (LeIF) and patient PBMC responses to rLeIF. Patients with mucosal and self-healing cutaneous disease had significantly higher proliferative responses than those with cutaneous lesions. Whereas the parasite lysate stimulated patient PBMC to produce a mixed Th1/Th2-type cytokine profile, LeIF stimulated the production of interferon gamma (IFN-gamma), interleukin 2 (IL-2), and tumor necrosis factor alpha but not IL-4 or IL-10. Recombinant LeIF (rLeIF) downregulated both IL-10 mRNA in the "resting" PBMC of leishmaniasis patients and LPS-induced IL-10 production by patient PBMC. rLeIF also stimulated the production of IL-12 in cultured PBMC from both patients and uninfected individuals. The production of IFN-gamma by patient PBMC stimulated with either rLeIF or parasite lysate was IL-12 dependent, whereas anti-IFN-gamma monoclonal antibody only partially blocked the LeIF-induced production of IL-12. In vitro production of both IFN-gamma and IL-12 was abrogated by exogenous human recombinant IL-10. Therefore, we have identified a recombinant leishmanial antigen that elicits IL-12 production and Th1-type responses in patients as well as IL-12 production in normal human PBMC.

SUBMITTER: Skeiky YA

PROVIDER: S-EPMC2191953 | biostudies-other | 1995 Apr

REPOSITORIES: biostudies-other

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A recombinant Leishmania antigen that stimulates human peripheral blood mononuclear cells to express a Th1-type cytokine profile and to produce interleukin 12.

Skeiky Y A YA Guderian J A JA Benson D R DR Bacelar O O Carvalho E M EM Kubin M M Badaro R R Trinchieri G G Reed S G SG

The Journal of experimental medicine 19950401 4

Leishmania braziliensis causes cutaneous and mucosal leishmaniasis in humans. Most patients with cutaneous leishmaniasis heal spontaneously and may therefore have developed protective immunity. There appears to be a mixed cytokine profile associated with active cutaneous or mucosal disease, and a dominant T helper (Th)1-type response associated with healing. Leishmanial antigens that elicit these potent proliferative and cytokine responses from peripheral blood mononuclear cells (PBMC) are now b ...[more]

PMID: 7699334

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Project description:BACKGROUND:Psoriasis is a T cell-mediated autoimmune disease in patients with elevated levels of proinflammatory cytokines belonging mainly to the Th1 pathway. We investigated whether treatment of psoriasis patients with methotrexate (MTX), along with micronutrients, modulated mRNA expression of Th1 and Th2 components and whether expression of these components correlated with psoriasis severity. METHODS:Thirty plaque-type psoriasis patients with Psoriasis Area and Severity Index (PASI) scores greater than 10 were recruited; these were 15 non-micronutrients taking- (NMT) patients treated with MTX daily (0.2-0.3 mg/kg/week), and 15 micronutrients taking- (MT) patients treated with MTX plus a micronutrient supplement daily, for 12 weeks. Blood samples were collected immediately before treatment (baseline) and after 12 weeks of treatment. Taqman quantitative real-time polymerase chain reaction (qPCR) was applied to analyze the expression of the Th1 components T-bet, interleukin-12 (IL-12), and interferon-gamma (IFN-?), and the Th2 components GATA-3 and interleukin-4 (IL-4). Disease severity was measured using the PASI scoring system. RESULTS:Significant clinical improvement in the MT group coincided with significant down-regulation of Th1 and up-regulation of Th2 markers (P<0.05). With respect to the PASI-75, (defined as a 75% or greater reduction in the PASI score) cut-off point, expression of IFN-? in the MT group with PASI scores above 75 was significantly less than that of patients in the NMT group (P=0.05). Also, GATA3 and IL-4 mRNA expression in the MT group with PASI scores greater than above 75 was significantly greater than that of patients in the NMT group (P=0.05 and 0.04, respectively). CONCLUSION:Based on significant attenuation of the PASI score, which correlated with upregulation of Th2 pathway markers in the MT group, we recommend administration of micronutrients combined with MTX for psoriasis patients. Our results contribute to a better understanding of methotrexate immunepathogenesis mechanisms and their correlations to clinical responses in psoriasis.

Dataset Information

A recombinant Leishmania antigen that stimulates human peripheral blood mononuclear cells to express a Th1-type cytokine profile and to produce interleukin 12.

Publications

A recombinant Leishmania antigen that stimulates human peripheral blood mononuclear cells to express a Th1-type cytokine profile and to produce interleukin 12.

Similar Datasets

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