title: Mononuclear cells from patients recovered from cutaneous leishmaniasis respond to Leishmania major amastigote class I nuclease with a predominant Th1-like response.
abstract: The Leishmania major amastigote class I nuclease (LmaCIN) is a developmentally regulated protein that is highly expressed in the amastigote stage of L. major. This protein is homologous to the P4 nuclease of L. pifanoi, which has been shown to induce protective immune response in a murine model. To evaluate LmaCIN as a potential human vaccine candidate, cellular immune responses to recombinant LmaCIN were examined in individuals recovered from Old World cutaneous leishmaniasis. Peripheral blood mononuclear cells (PBMC) from patients recovered from L. major infection were cultured either with recombinant LmaCIN or autoclaved L. major (ALM) as control. rLmaCIN induced significant proliferation of PBMC from 90% of recovered patients. Phenotypic analysis of proliferating cells showed that CD8(+) cells were the predominant cell type proliferating in response to rLmaC1N. Screening of culture supernatants for cytokines showed that rLmaCIN induced high levels of interferon (IFN)-gamma (mean +/- s.e.m.: 1398 +/- 179 pg/ml) associated with little interleukin (IL)-10 and little or no IL-5 production. These findings show that LmaCIN is immunogenic in humans during L. major infection and that it can elicit immunological responses relevant to immunoprophylaxis of leishmaniasis.
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Farajnia
authors.forename: F
authors.initials: F
authors.lastname: Mahboudi
authors.forename: S
authors.initials: S
authors.lastname: Ajdari
authors.forename: N E
authors.initials: NE
authors.lastname: Reiner
authors.forename: A
authors.initials: A
authors.lastname: Kariminia
authors.forename: M H
authors.initials: MH
authors.lastname: Alimohammadian
mesh_terms: D000704:Analysis of Variance; D000953:Antigens, Protozoan / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D049109:Cell Proliferation; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000628:therapy; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D016052:Protozoan Vaccines / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000494:pharmacology
chemical_list: D000953:Antigens, Protozoan; D015848:Interleukin-5; D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic; D016753:Interleukin-10; D007371:Interferon-gamma
references.citation: J Exp Med. 2001 Nov 19;194(10):1497-506
references.pmid: 11714756
references.citation: Clin Exp Immunol. 2001 May;124(2):255-61
references.pmid: 11422202
references.citation: Clin Diagn Lab Immunol. 2002 Mar;9(2):251-6
references.pmid: 11874860
references.citation: J Immunol. 2002 Apr 15;168(8):3992-4000
references.pmid: 11937556
references.citation: Nat Rev Immunol. 2002 Nov;2(11):845-58
references.pmid: 12415308
references.citation: Parasitol Int. 2002 Dec;51(4):367-79
references.pmid: 12421635
references.citation: Vaccine. 2002 Dec 13;21(3-4):174-80
references.pmid: 12450691
references.citation: Clin Exp Immunol. 2003 May;132(2):316-22
references.pmid: 12699423
references.citation: Infect Immun. 2003 Jun;71(6):3172-82
references.pmid: 12761096
references.citation: Infect Immun. 2003 Nov;71(11):6270-8
references.pmid: 14573646
references.citation: Trends Parasitol. 2003 Nov;19(11):502-8
references.pmid: 14580961
references.citation: Int J Parasitol. 2004 Jul;34(8):899-908
references.pmid: 15217728
references.citation: Infect Immun. 1988 Dec;56(12):3272-9
references.pmid: 3182080
references.citation: Trans R Soc Trop Med Hyg. 1989 Mar-Apr;83(2):189-92
references.pmid: 2609368
references.citation: Exp Parasitol. 1990 May;70(4):427-35
references.pmid: 2182337
references.citation: J Biol Chem. 1990 May 5;265(13):7236-42
references.pmid: 2158995
references.citation: Immunol Today. 1991 Mar;12(3):A58-61
references.pmid: 1829891
references.citation: Mol Biochem Parasitol. 1991 Jul;47(1):109-17
references.pmid: 1857379
references.citation: Rev Infect Dis. 1991 Sep-Oct;13(5):1009-17
references.pmid: 1962075
references.citation: Biochem J. 1992 Jul 1;285 ( Pt 1):41-6
references.pmid: 1322126
references.citation: Curr Opin Immunol. 1992 Aug;4(4):413-8
references.pmid: 1356346
references.citation: Infect Immun. 1993 Jul;61(7):2952-9
references.pmid: 8514400
references.citation: J Clin Invest. 1993 Jul;92(1):324-9
references.pmid: 8326000
references.citation: Infect Immun. 1993 Sep;61(9):3730-8
references.pmid: 8359894
references.citation: Clin Exp Immunol. 1993 Dec;94(3):516-21
references.pmid: 7902789
references.citation: J Clin Invest. 1993 Dec;92(6):2626-32
references.pmid: 8254019
references.citation: Trans R Soc Trop Med Hyg. 1993 Sep-Oct;87(5):550-1
references.pmid: 8266406
references.citation: Infect Immun. 1994 Jun;62(6):2575-81
references.pmid: 8188380
references.citation: Clin Exp Immunol. 1994 Jun;96(3):410-5
references.pmid: 8004809
references.citation: Eur J Immunol. 1994 Nov;24(11):2813-7
references.pmid: 7957573
references.citation: J Exp Med. 1995 Apr 1;181(4):1527-37
references.pmid: 7699334
references.citation: Mol Biochem Parasitol. 1995 Apr;71(1):51-63
references.pmid: 7630383
references.citation: Infect Immun. 1995 Sep;63(9):3559-66
references.pmid: 7642292
references.citation: Infect Immun. 1995 Nov;63(11):4261-7
references.pmid: 7591056
references.citation: Infect Immun. 1995 Dec;63(12):4894-9
references.pmid: 7591152
references.citation: Exp Parasitol. 1996 Nov;84(2):144-55
references.pmid: 8932764
references.citation: J Immunol. 1996 Dec 1;157(11):5034-41
references.pmid: 8943412
references.citation: Infect Immun. 1998 Jul;66(7):3100-5
references.pmid: 9632572
references.citation: Infect Immun. 1998 Jul;66(7):3279-89
references.pmid: 9632596
references.citation: Nat Med. 1998 Dec;4(12):1409-15
references.pmid: 9846579
references.citation: Parasite Immunol. 1999 Apr;21(4):211-8
references.pmid: 10320618
references.citation: J Biol Chem. 2000 May 26;275(21):16366-72
references.pmid: 10748102
references.citation: J Immunol. 2000 Jul 15;165(2):915-24
references.pmid: 10878366
references.citation: J Infect Dis. 2000 Aug;182(2):570-8
references.pmid: 10915091
references.citation: Cytokine. 2000 Aug;12(8):1228-31
references.pmid: 10930301
references.citation: J Biol Chem. 2000 Dec 1;275(48):37789-97
references.pmid: 10969068
references.citation: J Immunol. 2001 Jan 15;166(2):1141-7
references.pmid: 11145695
references.citation: Annu Rev Immunol. 2001;19:683-765
references.pmid: 11244051
references.citation: J Immunol. 2001 Apr 15;166(8):5122-8
references.pmid: 11290794
references.citation: Int J Parasitol. 2002 Apr;32(4):449-59
references.pmid: 11849641