High resolution radiographic and fine immunologic definition of TB disease progression in the rhesus macaque

Lewinsohn, David; Tydeman, Ian S.; Frieder, Marisa; Grotzke, Jeff E.; Lines, Rebecca A.; Ahmed, Sheela; Prongay, Kamm; Primack, Steven L.; Colgin, Lois M.A.; Lewis, Anne D.; Lewinsohn, Deborah A.

doi:10.1016/j.micinf.2006.07.007

Cited by 60 publications

(60 citation statements)

References 23 publications

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“…Previous work has shown that CD8 1 T cells preferentially recognize dendritic cells harboring intracellular bacteria, especially cells heavily infected with Mtb (9). Although the in vivo relevance of such observations remains difficult to assess, the magnitude of the CD8 1 T-cell response has been shown to correlate with mycobacterial burden in TB animal models (19,20). Moreover, these findings mirror work shown in HIV where there is a robust association between CD8…”

Section: Discussionsupporting

confidence: 54%

CD8⁺T Cells Provide an Immunologic Signature of Tuberculosis in Young Children

Lancioni

Nyendak²,

Kiguli

et al. 2012

Am J Respir Crit Care Med

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Rationale: The immunologic events surrounding primary Mycobacterium tuberculosis infection and development of tuberculosis remain controversial. Young children who develop tuberculosis do so quickly after first exposure, thus permitting study of immune response to primary infection and disease. We hypothesized that M. tuberculosis-specific CD8 1 T cells are generated in response to high bacillary loads occurring during tuberculosis. Objectives: To determine if M. tuberculosis-specific T cells are generated among healthy children exposed to M. tuberculosis and children with tuberculosis.Methods: Enzyme-linked immunosorbent spot assays were used to measure IFN-g production in response to M. tuberculosis-specific proteins ESAT-6/CFP-10 by peripheral blood mononuclear cells and CD8 1 T cells isolated from Ugandan children hospitalized with tuberculosis (n ¼ 96) or healthy tuberculosis contacts (n ¼ 62). Measurements and Main Results: The proportion of positive CD8 1 T-cell assays and magnitude of CD81 T-cell responses were significantly greater among young (,5 yr) tuberculosis cases compared with young contacts (P ¼ 0.02, Fisher exact test, P ¼ 0.01, Wilcoxon rank-sum, respectively). M. tuberculosis-specific T-cell responses measured in peripheral blood mononuclear cells were equivalent between groups. Conclusions: Among young children, M. tuberculosis-specific CD8 1 T cells develop in response to high bacillary loads, as occurs during tuberculosis, and are unlikely to be found after M. tuberculosis exposure. T-cell responses measured in peripheral blood mononuclear cells are generated after M. tuberculosis exposure alone, and thus cannot distinguish exposure from disease. In young children, IFN-g-producing M. tuberculosis-specific CD8 1 T cells provide an immunologic signature of primary M. tuberculosis infection resulting in disease.

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Section: Discussionsupporting

confidence: 54%

CD8⁺T Cells Provide an Immunologic Signature of Tuberculosis in Young Children

Lancioni

Nyendak²,

Kiguli

et al. 2012

Am J Respir Crit Care Med

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“…A series of subsequent investigations were dedicated to macaque research to assess novel TB vaccines and drugs, as well as to gain an understanding of the pathogenesis of M. tuberculosis infection and reactivation. Figures 2 and 3 abridge the RM (13,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43) and CM (10,15,25,(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59) models of experimental M. tuberculosis infection after the Golden Age, from 2001 to 2014.…”

Section: Historical Outlook On Macaque Modelsmentioning

confidence: 99%

“…In an attempt to improve the methods to monitor the progression of TB disease, Helke et al (27) from the Oregon NPRC showed that use of highresolution radiographic and fine immunologic studies helped define the disease status in RM as in humans. Namely, computed tomography (CT) evaluation and M. tuberculosis-specific T cell frequencies measured by enzyme-linked immunosorbent spot (ELISPOT) assays correlated well with the bacterial burden and severity of disease (27).…”

Section: Rhesus Macaquesmentioning

confidence: 99%

Monkey Models of Tuberculosis: Lessons Learned

Peña

2015

Infect Immun

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bThe use of animal models has been invaluable for studying the pathogenesis of Mycobacterium tuberculosis infection, as well as for testing the efficacy of vaccines and drug regimens for tuberculosis. Among the applied animal models, nonhuman primates, particularly macaques, share the greatest anatomical and physiological similarities with humans. As such, macaque models have been used for investigating tuberculosis pathogenesis and preclinical testing of drugs and vaccines. This review focuses on published major studies which illustrate how the rhesus and cynomolgus macaques have enriched and may continue to advance the field of global tuberculosis research.

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“…We truly need such information to decide whether two vaccines compared by using monkeys would produce as decisive a result as the same vaccines compared by using rabbits. Such "ratios" cannot be obtained if monkeys are challenged intratracheally (59,103) or bronchoscopically (17,60), because these procedures deposit numerous tubercle bacilli into one locale.…”

Section: Tuberculosis In Nonhuman Primatesmentioning

confidence: 99%

Perspectives on Clinical and Preclinical Testing of New Tuberculosis Vaccines

Dannenberg

2010

Clin Microbiol Rev

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SUMMARY This review hopes to improve the selection of new tuberculosis (TB) vaccines by providing several perspectives on the immunization of humans, mice, guinea pigs, rabbits, and monkeys which have not usually been considered. (i) In human TB vaccine trials, the low rate of healing of Mycobacterium bovis BCG lesions (used as the control group) would distinguish individuals who might be helped by vaccination from the 95% who do not need it and would make these trials more conclusive. (ii) The rabbit immune response to Mycobacterium tuberculosis is much more effective in arresting tuberculosis than those of other laboratory animals, so pulmonary tubercle counting in rabbits should be included in all preclinical TB vaccine testing. (iii) Both delayed-type hypersensitivity (DTH) and cell-mediated immunity (CMI) are necessary to control the growth of M. tuberculosis. The testing of new TB vaccines in mice or in guinea pigs may not detect important antigens needed for human immunization. Mice respond poorly to tuberculin-like antigens that cause DTH. Guinea pigs respond poorly to antigens that cause CMI. Rabbits and humans respond well to both DTH and CMI antigens. Since monkeys are very susceptible to M. tuberculosis, they may not be as useful as rabbits for preclinical vaccine evaluation. (iv) Critical antigens (possibly ESAT-6 or CFP-10) might increase the immunity of the host to a greater extent than that produced by a natural M. tuberculosis infection and therefore would be useful in both prophylaxis and immunotherapy. Such critical antigens would increase the host's ability to neutralize key components of M. tuberculosis that enable it to survive in both laboratory animals and humans.

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High resolution radiographic and fine immunologic definition of TB disease progression in the rhesus macaque

Cited by 60 publications

References 23 publications

CD8⁺T Cells Provide an Immunologic Signature of Tuberculosis in Young Children

CD8⁺T Cells Provide an Immunologic Signature of Tuberculosis in Young Children

Monkey Models of Tuberculosis: Lessons Learned

Perspectives on Clinical and Preclinical Testing of New Tuberculosis Vaccines

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High resolution radiographic and fine immunologic definition of TB disease progression in the rhesus macaque

Cited by 60 publications

References 23 publications

CD8+T Cells Provide an Immunologic Signature of Tuberculosis in Young Children

CD8+T Cells Provide an Immunologic Signature of Tuberculosis in Young Children

Monkey Models of Tuberculosis: Lessons Learned

Perspectives on Clinical and Preclinical Testing of New Tuberculosis Vaccines

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Product

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CD8⁺T Cells Provide an Immunologic Signature of Tuberculosis in Young Children

CD8⁺T Cells Provide an Immunologic Signature of Tuberculosis in Young Children