title: Analysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization.
abstract: Analysis of tissue lesions of the major reactional states of leprosy was undertaken to study the immune mechanisms underlying regulation of cell-mediated immunity and delayed-type hypersensitivity (DTH) in man. In situ hybridization hybridization of reversal reaction biopsy specimens for INF-gamma mRNA expression revealed a 10-fold increase in specific mRNA-containing cells over that observed in unresponsive lepromatous patients. Expression of huHF serine esterase, a marker for T cytotoxic cells, were fourfold increased in reversal reaction and tuberculoid lesions above that detected in unresponsive lepromatous individuals. Immunohistology of reversal reactions confirmed a selective increase of Th and T cytotoxic cells in the cellular immune response. Of interest, the microanatomic location of these serine esterase mRNA-containing cells was identical to the distribution of CD4+ cells. Analysis of erythema nodosum leprosum (ENL) lesions revealed differences in the underlying immune processes in comparison with reversal reaction lesions. Although phenotypic Th cells predominated in ENL lesions, IFN-gamma and serine esterase gene expression were markedly reduced. We suggest that reversal reactions represent a hyperimmune DTH response characterized by a selective increase of CD4+ IFN-gamma producing cells and T cytotoxic cells, which result in the clearing of bacilli and concomitant tissue damage. In contrast, ENL reactions may be viewed as a transient diminution of Ts cells and activity leading to a partial and transient augmentation in cell-mediated immunity, perhaps sufficient to result in antibody and immune complex formation, but insufficient to clear bacilli from lesions.
authors.affiliation: Department of Pathology, University of Southern California, School of Medicine, Los Angeles 90033.
authors.forename: C L
authors.initials: CL
authors.lastname: Cooper
authors.forename: C
authors.initials: C
authors.lastname: Mueller
authors.forename: T A
authors.initials: TA
authors.lastname: Sinchaisri
authors.forename: C
authors.initials: C
authors.lastname: Pirmez
authors.forename: J
authors.initials: J
authors.lastname: Chan
authors.forename: G
authors.initials: G
authors.lastname: Kaplan
authors.forename: S M
authors.initials: SM
authors.lastname: Young
authors.forename: I L
authors.initials: IL
authors.lastname: Weissman
authors.forename: B R
authors.initials: BR
authors.lastname: Bloom
authors.forename: T H
authors.initials: TH
authors.lastname: Rea
authors.forename: R L
authors.initials: RL
authors.lastname: Modlin
mesh_terms: D004950:Esterases / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D006968:Hypersensitivity, Delayed; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000235:genetics*; D007918:Leprosy / Q000276:immunology* / Q000473:pathology; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D007371:Interferon-gamma; D004950:Esterases; C022635:serine esterase