title: Type 1- and type 2-like lesional skin-derived Mycobacterium leprae-responsive T cell clones are characterized by coexpression of IFN-gamma/TNF-alpha and IL-4/IL-5/IL-13, respectively.
abstract: In an earlier study, we generated a large number of Mycobacterium leprae-responsive and M. leprae-nonresponsive T cell clones (TCC) from the lesional skin of immunologic unstable borderline leprosy patients. In that study, we divided TCC into type 1- and type 2-like on the basis of their IFN-gamma and IL-4 expression. To explore whether other cytokines are coproduced along with IFN-gamma and IL-4, we investigated the secretion of a panel of other cytokines (TNF-alpha, IL-5, IL-6, IL-10, and IL-13) by a large number of these TCC. Upon analysis of 139 M. leprae-responsive TCC, we observed a positive correlation in the coproduction of IFN-gamma/TNF-alpha (r = 0.81), and in that of IL-4/IL-5 (r = 0.83), IL-4/IL-13 (r = 0.80), and IL-5/IL-13 (r = 0.82). Polarized type 1-like TCC produced dominantly IFN-gamma/TNF-alpha, and polarized type 2-like TCC predominantly IL-4/IL-5/IL-13. Most type 0-like TCC produced both sets of cytokines. In contrast, type 1- and type 2-like subsets of M. leprae-nonresponsive TCC (n = 58) did not show the same coexpression of these cytokines. Furthermore, when the differential expression of a broad panel of cytokines by individual M. leprae-responsive TCC is considered, it appeared that additional phenotypes could be recognized. These results suggested that distinct isotypes of type 1- and type 2-like T cells, based on the secretion of a panel of cytokines, may reflect M. leprae-specific characteristics.
authors.affiliation: Department of Dermatology, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: C E
authors.initials: CE
authors.lastname: Verhagen
authors.forename: T C
authors.initials: TC
authors.lastname: van der Pouw Kraan
authors.forename: A A
authors.initials: AA
authors.lastname: Buffing
authors.forename: M A
authors.initials: MA
authors.lastname: Chand
authors.forename: W R
authors.initials: WR
authors.lastname: Faber
authors.forename: L A
authors.initials: LA
authors.lastname: Aarden
authors.forename: P K
authors.initials: PK
authors.lastname: Das
mesh_terms: D002999:Clone Cells; D004797:Enzyme-Linked Immunosorbent Assay / Q000706:statistics & numerical data; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis*; D018793:Interleukin-13 / Q000096:biosynthesis / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism; D015848:Interleukin-5 / Q000096:biosynthesis / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis* / Q000378:metabolism; D007918:Leprosy / Q000276:immunology* / Q000473:pathology; D009166:Mycobacterium leprae / Q000276:immunology*; D012867:Skin / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D018709:Statistics, Nonparametric; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D018793:Interleukin-13; D015848:Interleukin-5; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma