The histology of the Mitsuda reaction and its significance

Thomas, John B.; Joseph, Mary; Ramanujam, K; Chacko, C. J. G.; Job, C. K.

doi:10.5935/0305-7518.19800035

Cited by 8 publications

(13 citation statements)

References 1 publication

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“…Improved tools to monitor the extent of M. leprae exposure within communities would be a major help to control programs, allowing their efforts to be focused in areas of greatest need. The existing reagents, lepromin and leprosin, contain cross-reactive mycobacterial antigens and can induce positive skin test responses in BCG-vaccinated individuals (11,28). A number of current initiatives therefore aim to develop new skin test reagents for leprosy.…”

Section: Discussionmentioning

confidence: 99%

A Postgenomic Approach to Identification ofMycobacterium leprae-Specific Peptides as T-Cell Reagents

Dockrell

Brahmbhatt

Robertson³

et al. 2000

Infect Immun

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To identify Mycobacterium leprae-specific human T-cell epitopes, which could be used to distinguish exposure to M. leprae from exposure to Mycobacterium tuberculosis or to environmental mycobacteria or from immune responses following Mycobacterium bovis BCG vaccination, 15-mer synthetic peptides were synthesized based on data from the M. leprae genome, each peptide containing three or more predicted HLA-DR binding motifs. Eighty-one peptides from 33 genes were tested for their ability to induce T-cell responses, using peripheral blood mononuclear cells (PBMC) from tuberculoid leprosy patients (n ‫؍‬ 59) and healthy leprosy contacts (n ‫؍‬ 53) from Brazil, Ethiopia, Nepal, and Pakistan and 20 United Kingdom blood bank donors. Gamma interferon (IFN-␥) secretion proved more sensitive for detection of PBMC responses to peptides than did lymphocyte proliferation. Many of the peptides giving the strongest responses in leprosy donors compared to subjects from the United Kingdom, where leprosy is not endemic, have identical, or almost identical, sequences in M. leprae and M. tuberculosis and would not be suitable as diagnostic tools. Most of the peptides recognized by United Kingdom donors showed promiscuous recognition by subjects expressing differing HLA-DR types. The majority of the novel T-cell epitopes identified came from proteins not previously recognized as immune targets, many of which are cytosolic enzymes. Fifteen of the tested peptides had >5 of 15 amino acid mismatches between the equivalent M. leprae and M. tuberculosis sequences; of these, eight gave specificities of >90% (percentage of United Kingdom donors who were nonresponders for IFN-␥ secretion), with sensitivities (percentage of responders) ranging from 19 to 47% for tuberculoid leprosy patients and 21 to 64% for healthy leprosy contacts. A pool of such peptides, formulated as a skin test reagent, could be used to monitor exposure to leprosy or as an aid to early diagnosis.The completion of the sequencing of the genome of Mycobacterium tuberculosis (7) and the availability of almost 98% of the genome sequence of Mycobacterium leprae (http://www .sanger.ac.uk) provide a unique opportunity to identify specific antigens within these pathogens, which could be used as diagnostic tools. One approach, which has been used previously to develop M. tuberculosis-specific diagnostic antigens, is to identify genes present in M. tuberculosis which have been deleted from Mycobacterium bovis BCG (20) Previous studies of the human T-cell response in leprosy patients have identified a number of antigens that induce T-cell responses, measured by lymphocyte proliferation or gamma interferon (IFN-␥) secretion, in patients with tuberculoid leprosy. Such antigens include the M. leprae 70-kDa, 65-kDa, 45-kDa, 35-kDa, 18-kDa, and 10-kDa antigens (1,2,6,12,16,29,31). The members of the heat shock family of proteins are highly conserved, and homologues of the M. leprae 70-kDa, 65-kDa, and 10-kDa antigens show over 90% homology between M. leprae and M. tuberculosis. It is the...

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Section: Discussionmentioning

confidence: 99%

A Postgenomic Approach to Identification ofMycobacterium leprae-Specific Peptides as T-Cell Reagents

Dockrell

Brahmbhatt

Robertson³

et al. 2000

Infect Immun

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“…The existing diagnostic skin test reagents for leprosy, lepromin and leprosin, are prepared from whole autoclaved M. leprae and from the soluble fraction of M. leprae, respectively, and contain many mycobacterial antigens shared with other species (20). A more specific skin test reagent for leprosy would be a highly desirable diagnostic tool.…”

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confidence: 99%

Identification and Characterization of the ESAT-6 Homologue ofMycobacterium lepraeand T-Cell Cross-Reactivity withMycobacterium tuberculosis

Geluk¹,

Meijgaarden²,

Franken³

et al. 2002

Infect Immun

119

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In this paper we describe identification and characterization of Mycobacterium leprae ESAT-6 (L-ESAT-6), the homologue of M. tuberculosis ESAT-6 (T-ESAT-6). T-ESAT-6 is expressed by all pathogenic strains belonging to the M. tuberculosis complex but is absent from virtually all other mycobacterial species, and it is a promising antigen for immunodiagnosis of tuberculosis (TB). Therefore, we analyzed whether L-ESAT-6 is a similarly powerful tool for the study of leprosy by examining T-cell responses against L-ESAT-6 in leprosy patients, TB patients, and exposed or nonexposed healthy controls from areas where leprosy and TB are endemic and areas where they are not endemic. L-ESAT-6 was recognized by T cells from leprosy patients, TB patients, individuals who had contact with TB patients, and healthy individuals from an area where TB and leprosy are endemic but not by T cells from individuals who were not exposed to M. tuberculosis and M. leprae. Moreover, leprosy patients who were not responsive to M. leprae failed to respond to L-ESAT-6. A very similar pattern was obtained with T-ESAT-6. These results show that L-ESAT-6 is a potent M. leprae antigen that stimulates T-celldependent gamma interferon production in a large proportion of individuals exposed to M. leprae. Moreover, our results suggest that there is significant cross-reactivity between T-ESAT-6 and L-ESAT-6, which has implications for the use of ESAT-6 as tool for diagnosis of leprosy and TB in areas where both diseases are endemic.Tuberculosis (TB) and leprosy are major public health problems in the developing world. One-third of the world's population is infected with Mycobacterium tuberculosis, and around 2 million individuals suffer from leprosy (9). Many studies have shown that early culture filtrate proteins of M. tuberculosis can be dominant target antigens for CD4 ϩ Th1 cells both in animal models of TB (1, 2, 5, 12, 13) and in humans. One of these secreted antigens, called T-ESAT-6, is a 10-kDa protein which is present in M. tuberculosis and virulent M. bovis but not in M. bovis BCG, and this protein could not be detected in M. leprae, M. avium, M. scrofulaceum, M. intracellulare, M. fortuitum, and M. xenopi (3, 11). Indeed, when the T-ESAT-6 protein was used, TB-infected cattle could be distinguished from cattle sensitized by environmental mycobacteria (15), and in humans T-ESAT-6 and T-ESAT-6-derived peptides were shown to be very efficiently and specifically recognized by individuals exposed to M. tuberculosis (4,14,16,21). The gene for ESAT-6 (Rv3875) is in a region of the M. tuberculosis genome, designated RD1, that is indeed absent from M. bovis BCG and most nontuberculous mycobacteria (NTM).The existing diagnostic skin test reagents for leprosy, lepromin and leprosin, are prepared from whole autoclaved M. leprae and from the soluble fraction of M. leprae, respectively, and contain many mycobacterial antigens shared with other species (20). A more specific skin test reagent for leprosy would be a highly desirable diagnostic tool. Becaus...

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“…In tuberculoid leprosy patients the skin test induces formation of localized tuberculoid type granulomas over the course of 28 days. These lesions are essentially indentical to those seen in naturally occurring lesions in the same patients (16,17,19). Lepromatous patients, on the other hand, fail to form organized granulomas in response to the same antigen challenge.…”

Section: Introductionmentioning

confidence: 66%

“…The lepromin skin test, consisting of an intradermal injection of killed M. leprae pro vides an opportunity to observe host reponse to the organism within a 28 day period (12)(13)(14)(15)(16)(17)(18). In tuberculoid leprosy patients the skin test induces formation of localized tuberculoid type granulomas over the course of 28 days.…”

Section: Introductionmentioning

confidence: 99%

Lepromin stimulates interleukin-2 production and interleukin-2 receptor expression in situ in lepromatous leprosy patients

Bj¹,

Haregewoin²,

W³

et al. 1986

Leprosy Review

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The histology of the Mitsuda reaction and its significance

Cited by 8 publications

References 1 publication

A Postgenomic Approach to Identification ofMycobacterium leprae-Specific Peptides as T-Cell Reagents

A Postgenomic Approach to Identification ofMycobacterium leprae-Specific Peptides as T-Cell Reagents

Identification and Characterization of the ESAT-6 Homologue ofMycobacterium lepraeand T-Cell Cross-Reactivity withMycobacterium tuberculosis

Lepromin stimulates interleukin-2 production and interleukin-2 receptor expression in situ in lepromatous leprosy patients

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