02777nas a2200409   4500000000100000008004100001260001600042653001400058653003100072653001100103653003000114653002500144653002100169653001200190653003100202653001900233653001800252653003400270653003000304100001500334700001400349700001900363700001300382700001100395700001300406700001400419700001700433700001400450700001200464700001500476245011300491300001200604490000800616050001500624520171400639022001402353       1989                            d  c1989 May 0110aEsterases10aGene Expression Regulation10aHumans10aHypersensitivity, Delayed10aImmunohistochemistry10aInterferon-gamma10aleprosy10aNucleic Acid Hybridization10aRNA, Messenger10aT-Lymphocytes10aT-Lymphocytes, Helper-Inducer10aT-Lymphocytes, Regulatory1 aCooper C L1 aMueller C1 aSinchaisri T A1 aPirmez C1 aChan J1 aKaplan G1 aYoung S M1 aWeissman I L1 aBloom B R1 aRea T H1 aModlin R L00aAnalysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization.  a1565-810 v169  aCOOPER19893 a<p>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.</p>  a0022-1007