Delayed hypersensitivity reactions by the mycobacterial antigen A60 and cutaneous testing in tuberculosis

Benoit, Claudette; Beschin, Alain; Desmecht, M.; Dekeyser, P.; Cocito, Carlo

doi:10.1007/bf00203306

Cited by 20 publications

(13 citation statements)

References 24 publications

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“…Foot-pad thickness was measured with a special caiiper (type ODI-OOT. ODI-TEST, Kroeplin, Germany) before and at different intervals after foot-pad injection [18].…”

Section: Methodsmentioning

confidence: 99%

“…To explore in vivo the status of cell-mediated immunity during cancer development, type IV delayed hypersensitivity reactions (DHR) against A60 were elicited in all groups [18].…”

Section: The Effects Of Tumour Development and Immunotherapy On Delaymentioning

confidence: 99%

“…The role of macrophages and TIL in cancer immunology are well studied [27,[36][37][38][39][40][41]. It is known that A60 induces production of both IFN--> and IL-2 [15,18], which may account for the increase in infiltrating lymphocytes (IL-2 response) and of macrophages (IFN-7 response). In addition, the observation that some TIL respond to IL-2 and others to tumour antigens might account for the synergistic effect of A60 (aspecific activation) and of irradiated tumour cells (specific activation) (Table i and Fig.…”

Section: Histopathological Pattern Of Tumour Reactionmentioning

confidence: 99%

“…Characterization of the protein components of A60 is described in two recent publications [15,16]. The A60 complex (the TMA of Mycobacterium bovis BCG) proved to be immunodominant in tuberculosis, to elicit both humoral and cellular immune reactions [17,18], and to confer antituberculous immunity, a process occurring in two steps : one specific and lymphocyte-dependent, and the other aspecific and macrophage-dependent. We have recently shown that lymphocytes from A60-primed mice are able to induce macrophage activation in vitro, resulting in the prevention of intracellular mycobacterial proliferation [19].…”

Section: Introductionmentioning

confidence: 99%

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Alteration of the Immune Response During Cancer Development and Prevention by Administration of a Mycobacterial Antigen

Maes

Taper²,

Cocito³

1995

Scand J Immunol

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It has been shown previously that A60, an antigen complex of Mycobacterium bovis BCG, triggers humoral and cellular immune reactions in vivo and lymphocyte-dependent macrophage activation in vitro. In the present work, the ability of A60 to prevent murine tumour development, in conjunction or not with irradiated isologous cancer cells, was explored with Taper liver tumour (TLT), a mammary-derived neoplasm (EMT6), and Lewis lung carcinoma (3LL). Repeated injections of A60 prior to challenge reduced the incidence of EMT6 and 3LL solid tumours and increased life span. This effect was enhanced by simultaneous administration of gamma-irradiated cancer cells (80-100% suppression of EMT6 and 3LL tumour growth). In mice developing or rejecting tumours, the status of humoral and cellular immunity was evaluated by A60-based immunoassays. Tumor development was accompanied by a rapid decrease of both anti-A60 IgG titre in blood and A60-triggered delayed hypersensitivity reactions. Moreover, A60-induced T lymphocyte proliferation and macrophage-dependent autologous cancer cell cytolysis declined progressively during the course of tumour growth. In case of successful immunotherapy, a pattern similar to that of unchallenged controls was observed. Our results suggest that A60 promotes cancer rejection via tumour infiltration by lymphocytes and macrophages activated by A60-specific T lymphocytes. An increased processing of tumour-specific antigens and activation of tumour-infiltrating lymphocytes is induced by administration of irradiated cancer cells in conjunction with A60.

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“…Foot-pad thickness was measured with a special caiiper (type ODI-OOT. ODI-TEST, Kroeplin, Germany) before and at different intervals after foot-pad injection [18].…”

Section: Methodsmentioning

confidence: 99%

“…To explore in vivo the status of cell-mediated immunity during cancer development, type IV delayed hypersensitivity reactions (DHR) against A60 were elicited in all groups [18].…”

Section: The Effects Of Tumour Development and Immunotherapy On Delaymentioning

confidence: 99%

Section: Histopathological Pattern Of Tumour Reactionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Alteration of the Immune Response During Cancer Development and Prevention by Administration of a Mycobacterial Antigen

Maes

Taper²,

Cocito³

1995

Scand J Immunol

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“…The branched glycan core and lipid components have negligible antigenicity (23 (14,16,31,49,50,183). Sensitins, bacterial extracts used for cutaneous testing, contain TMA components that are partly responsible for the elicited DHR (79,92).…”

Section: Immunological Aspectsmentioning

confidence: 99%

Paratuberculosis

Cocito¹,

Gilot²,

Coene³

et al. 1994

Clin Microbiol Rev

269

232

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Paratuberculosis (Johne's disease) is a chronic, wasting, widespread mycobacteriosis of ruminants. It involves extensive mycobacterial shedding, which accounts for the high contagiousness, and ends with a fatal enteritis. Decreases in weight, milk production, and fertility produce severe economic loss. The DNA of the etiological agent (Mycobacterium paratuberculosis) has a base composition (66 to 67% G+C) within the range of that of mycobacteria (62 to 70% G+C), a size (4.4 x 10(6) to 4.7 x 10(6) bp) larger than that of most pathogenic mycobacteria (2.0 x 10(6) to 4.2 x 10(6) bp), and a high relatedness (> 90%) to Mycobacterium avium DNA. However, the DNAs of the two organisms can be distinguished by restriction fragment length polymorphism analysis. M. paratuberculosis genes coding for a transposase, a cell wall-associated protein (P34), and two heat shock proteins have been cloned and sequenced. Nucleic acid probes (two of which are species specific) are used, after PCR amplification, for M. paratuberculosis identification in stools and milk. As in leprosy, with disease progression, cellular immune reactions decrease and humoral immune reactions increase. Cutaneous testing with sensitins, lymphocyte proliferation assays, and cytokine tests are used to monitor cellular immune reactions in paratuberculosis, but these tests lack specificity. Complement fixation, immunodiffusion, and enzymometric tests based on antibodies to M. paratuberculosis extracts, to mycobacterial antigen complex A36, to glycolipids, and to proteins help identify affected cattle but are not species specific. The carboxyl-terminal portion of the 34-kDa cell wall-associated A36 protein (P34) carries species-specific B-cell epitopes and is the basis for an enzyme-linked immunosorbent assay. Diagnostic tests for paratuberculosis are also used in Crohn's disease, a chronic human ileitis mimicking Johne's disease, in which isolates identified as M. paratuberculosis have been found.

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Comparative cutaneous testing with purified protein derivative and the antigen complex A60 in vaccinated subjects and tuberculosis patients

Zou¹,

Zhang²,

Chen³

et al. 1995

Med Microbiol Immunol

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Some 840 bacille Calmette-Guérin (BCG)-vaccinated healthy controls and tuberculosis patients from two Chinese hospitals were submitted to comparative skin tests with purified protein derivative of tuberculin (PPD; as reference) and with the antigen complex A60 from Mycobacterium bovis BCG. In a first trial, including 581 persons (185 healthy juveniles, 180 healthy adults and 216 tuberculosis patients), a limited dose of A60 (1 microgram) was used. Performance of the A60 test was similar to that of 5 I.U. PPD for controls (cut-off values = 5 mm induration diameter), but lower than that seen for tuberculosis patients (10 mm cut-off values). A second survey was conducted on 259 persons (109 recently revaccinated healthy persons, considered as tuberculin-negative in the first trial, and 150 tuberculosis patients), using a higher dose of A60 (2 micrograms) and the same dose of PPD (5 I.U.). Similar results were obtained with the two tests in all cases, thus supporting the possibility of PPD replacement by A60 in cutaneous testing. The pattern of induration diameter distribution in healthy subjects who took part in the first testing round (64% positively rate) was displaced to the inactivity side (with a peak at 5 to 9-mm diameter), in comparison with the second round (90% positivity rate and peak at 10-14 mm). This indicates a progressive fading of cellular immunity reactions after BCG vaccination. In tuberculosis patients, no correlation was found among the following three parameters: positivity at cutaneous testing (with PPD or A60), titer of anti-A60 mycobacterial immunoglobulins in blood (IgG titer higher than cut-off line) and presence of mycobacteria in sputum.

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Delayed hypersensitivity reactions by the mycobacterial antigen A60 and cutaneous testing in tuberculosis

Cited by 20 publications

References 24 publications

Alteration of the Immune Response During Cancer Development and Prevention by Administration of a Mycobacterial Antigen

Alteration of the Immune Response During Cancer Development and Prevention by Administration of a Mycobacterial Antigen

Paratuberculosis

Comparative cutaneous testing with purified protein derivative and the antigen complex A60 in vaccinated subjects and tuberculosis patients

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