Analysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization

C. L. Cooper, C. Mueller, T. A. Sinchaisri, C. Pirmez, John Chan, G. Kaplan, S. M M Young, I. L. Weissman, B. R. Bloom, T. H. Rea, R. L. Modlin

Research output: Contribution to journalArticle

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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-γ 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-γ 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-γ 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 dimunution 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.

Original languageEnglish (US)
Pages (from-to)1565-1581
Number of pages17
JournalJournal of Experimental Medicine
Volume169
Issue number5
StatePublished - 1989
Externally publishedYes

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Delayed Hypersensitivity
Leprosy
In Situ Hybridization
Erythema Nodosum
Cellular Immunity
Messenger RNA
Bacillus
Antigen-Antibody Complex
Biopsy
Gene Expression
Antibodies

ASJC Scopus subject areas

  • Immunology

Cite this

Cooper, C. L., Mueller, C., Sinchaisri, T. A., Pirmez, C., Chan, J., Kaplan, G., ... Modlin, R. L. (1989). Analysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization. Journal of Experimental Medicine, 169(5), 1565-1581.

Analysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization. / Cooper, C. L.; Mueller, C.; Sinchaisri, T. A.; Pirmez, C.; Chan, John; Kaplan, G.; Young, S. M M; Weissman, I. L.; Bloom, B. R.; Rea, T. H.; Modlin, R. L.

In: Journal of Experimental Medicine, Vol. 169, No. 5, 1989, p. 1565-1581.

Research output: Contribution to journalArticle

Cooper, CL, Mueller, C, Sinchaisri, TA, Pirmez, C, Chan, J, Kaplan, G, Young, SMM, Weissman, IL, Bloom, BR, Rea, TH & Modlin, RL 1989, 'Analysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization', Journal of Experimental Medicine, vol. 169, no. 5, pp. 1565-1581.
Cooper, C. L. ; Mueller, C. ; Sinchaisri, T. A. ; Pirmez, C. ; Chan, John ; Kaplan, G. ; Young, S. M M ; Weissman, I. L. ; Bloom, B. R. ; Rea, T. H. ; Modlin, R. L. / Analysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization. In: Journal of Experimental Medicine. 1989 ; Vol. 169, No. 5. pp. 1565-1581.
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