title: Cytokine profile of circulating T cells of leprosy patients reflects both indiscriminate and polarized T-helper subsets: T-helper phenotype is stable and uninfluenced by related antigens of Mycobacterium leprae.
abstract: Cytokine profiles of circulating mononuclear cells were studied with the aim of delineating T-cell subsets in leprosy patients with active disease. Using reverse transcriptase-polymerase chain reaction (RT-PCR) for cytokine mRNA and enzyme-linked immunoassay (ELISA) for the secreted products, interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were studied. Three antigens, native Mycobacterium leprae, a recombinant antigen LSR/A15 of M. leprae and peptide 624 spanning 58-77 amino acids of the latter, were used to induce cytokine expression and release. Half of the subjects, irrespective of the clinical type or antigen used, showed a mixed T-helper type 0 (Th0)-like cytokine pattern, with evidence of the concomitant presence of IFN-gamma and IL-4. The remainder showed a polarized pattern based on the type of leprosy. Lepromatous patients with disseminated disease had Th2-type cytokines, with IL-4 but not IFN-gamma. In contrast, tuberculoid leprosy patients with localized disease showed a Th1-like profile, with the presence of IFN-gamma but not IL-4. Of interest was the stability of the Th phenotype for M. leprae-related antigens. Both the recombinant and the peptide antigens induced the same phenotype as the natural M. leprae bacillus in all except four of 45 leprosy patients.
authors.affiliation: Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: N
authors.initials: N
authors.lastname: Misra
authors.forename: A
authors.initials: A
authors.lastname: Murtaza
authors.forename: B
authors.initials: B
authors.lastname: Walker
authors.forename: N P
authors.initials: NP
authors.lastname: Narayan
authors.forename: R S
authors.initials: RS
authors.lastname: Misra
authors.forename: V
authors.initials: V
authors.lastname: Ramesh
authors.forename: S
authors.initials: S
authors.lastname: Singh
authors.forename: M J
authors.initials: MJ
authors.lastname: Colston
authors.forename: I
authors.initials: I
authors.lastname: Nath
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D001483:Base Sequence; D016207:Cytokines / Q000032:analysis* / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007918:Leprosy / Q000276:immunology*; D008969:Molecular Sequence Data; D009166:Mycobacterium leprae / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D017931:DNA Primers; D015850:Interleukin-6; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor