Region of Difference 1 Antigen–Specific CD4<sup>+</sup>Memory T Cells Correlate with a Favorable Outcome of Tuberculosis

Goletti, Delia; Butera, Ornella; Bizzoni, Federica; Casetti, Rita; Girardi, Enrico; Poccia, Fabrizio

doi:10.1086/507427

Cited by 117 publications

(109 citation statements)

References 30 publications

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“…It has been shown by flow cytometry that the T-cells responding to the RD antigens after 24-h stimulation are predominantly CD4 T-cells of an effector memory phenotype, characterised as being CD45RA-CCR7-, consistent with having recently encountered antigen in vivo [11,12,36,37]. In contrast, long-lived central memory T-cells that may persist even after successful treatment of tuberculosis [11,12,36,37,56,57] are less likely to release IFN-c after ,24 h of incubation and more likely to produce IL-2 [56].…”

Section: Sectionmentioning

confidence: 99%

“…In contrast, long-lived central memory T-cells that may persist even after successful treatment of tuberculosis [11,12,36,37,56,57] are less likely to release IFN-c after ,24 h of incubation and more likely to produce IL-2 [56].…”

Section: Sectionmentioning

confidence: 99%

“…Consequently, novel concepts have been investigated that include the use of different epitopes of RD antigens [11,12,36,37,58], readout different from IFN-c such as chemokines or cytokines [56,58], new antigens different from the RD genomic region, such as those defined as Rv1733c, Rv2029c, Rv2032, Rv2626c, Rv2627c, Rv2628 and HspX [29,[59][60][61], additional cytokines [56] or characteristic phenotypic markers [11,12,36,62]. Diagnostic sensitivity of IGRA can also be enhanced by incorporation of a novel RD1-encoded antigen, Rv3879c, without compromising diagnostic specificity [63].…”

Section: Sectionmentioning

confidence: 99%

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LTBI: latent tuberculosis infection or lasting immune responses toM. tuberculosis? A TBNET consensus statement

et al. 2009

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Tuberculosis control relies on the identification and preventive treatment of individuals who are latently infected with Mycobacterium tuberculosis. However, direct identification of latent tuberculosis infection is not possible. The diagnostic tests used to identify individuals latently infected with M. tuberculosis, the in vivo tuberculin skin test and the ex vivo interferon-c release assays (IGRAs), are designed to identify an adaptive immune response against, but not necessarily a latent infection with, M. tuberculosis. The proportion of individuals who truly remain infected with M. tuberculosis after tuberculin skin test or IGRA conversion is unknown. It is also uncertain how long adaptive immune responses towards mycobacterial antigens persist in the absence of live mycobacteria. Clinical management and public healthcare policies for preventive chemotherapy against tuberculosis could be improved, if we were to gain a better understanding on M. tuberculosis latency and reactivation. This statement by the TBNET summarises knowledge and limitations of the currently available tests used in adults and children for the diagnosis of latent tuberculosis infection.In summary, the main issue regarding testing is to restrict it to those who are known to be at higher risk of developing tuberculosis and who are willing to accept preventive chemotherapy.

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Section: Sectionmentioning

confidence: 99%

Section: Sectionmentioning

confidence: 99%

Section: Sectionmentioning

confidence: 99%

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LTBI: latent tuberculosis infection or lasting immune responses toM. tuberculosis? A TBNET consensus statement

et al. 2009

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“…New diagnostic approaches are needed that allow for a more targeted identification of patients at risk to develop TB. This may involve modifications of in vitro immunodiagnostic assays such as the use of novel stimulatory antigens [15,164,165], alternative biomarkers other than IFN-c [166][167][168][169][170][171][172], variations in incubation time [173,174], the readout system [9,12,13,175,176] or the clinical specimen instead of blood [177][178][179]. In addition, both for the detection of LTBI with a risk of reactivation and for suspected active TB, a novel approach based on a whole blood transcriptional signature could provide a biomarker system with high discriminative potential [180].…”

Section: Improvements In the Diagnosis Of Ltbi In Transplant Candidatmentioning

confidence: 99%

The risk of tuberculosis in transplant candidates and recipients: a TBNET consensus statement

Bumbăcea

Arend

Eyüboğlu³

et al. 2012

Eur Respir J

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233

261

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Tuberculosis (TB) is a possible complication of solid organ and hematopoietic stem cell transplantation. The identification of candidates for preventive chemotherapy is an effective intervention to protect transplant recipients with latent infection with Mycobacterium tuberculosis from progressing to active disease. The best available proxy for diagnosing latent infection with M. tuberculosis is the identification of an adaptive immune response by the tuberculin skin test or an interferon-c based ex vivo assay. Risk assessment in transplant recipients for the development of TB depends on, among other factors, the locally expected underlying prevalence of infection with M. tuberculosis in the target population. In areas of high prevalence, preventive chemotherapy for all transplant recipients may be justified without immunodiagnostic testing while in areas of medium and low prevalence, preventive chemotherapy should only be offered to candidates with positive M. tuberculosis-specific immune responses. The diagnosis of TB in transplant recipients can be challenging. Treatment of TB is often difficult due to substantial interactions between anti-TB drugs and immunosuppressive medications. This management guideline summarises current knowledge on the prevention, diagnosis and treatment of TB related to solid organ and hematopoietic stem cell transplantation and provides an expert consensus on questions where scientific evidence is still lacking. KEYWORDS: Guideline, management, Mycobacterium tuberculosis, transplantation, tuberculosis T uberculosis (TB) is caused by the pathogenic species of the Mycobacterium tuberculosis complex. Only a minority of individuals who develop an adaptive immune response following infection with M. tuberculosis will ever develop TB, with the actual risk depending on the extent to which the host immune system provides a successful or inadequate response [1,2]. Therefore, individuals with impaired immune response, such as solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, are more prone to develop TB than immunocompetent persons. TB in transplant recipients is more frequent compared to the general population (estimates from the last decades state 20-74 times as frequent in SOT [3,4] and twice as frequent in HSCT [5]), and more often fatal (up to 31% in SOT [6] and up to 50% in HSCT recipients [7]), thus adding effectiveness to interventions for its prevention, even in the face of difficulties, with treatment related to adverse drug events and drug-drug interactions. Active TB in transplant recipients can result from latent infection with M. tuberculosis (LTBI) in the transplant candidate or in the donor tissue, or from de novo post-transplant infection. These various scenarios prompt for targeted pre-transplant screening of both recipient and, if possible, donors to allow focused management of recipients selected for preventive intervention in the pre-and/or posttransplant period. The term ''preventive chemotherapy'' is used to denote treatmen...

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“…The reactivity of effector T cells would then decrease as a result of antigen withdrawal as the level of production of IFN-␥ from a single immune cell decreased after treatment. It has been shown that IFN-␥ production after 24 h of stimulation fades upon treatment and correlates with the development of memory T cells (10). Cytokine production might also change after treatment, as recently suggested (24).…”

Section: Discussionmentioning

confidence: 90%

T Cell Monitoring of Chemotherapy in Experimental Rat Tuberculosis

Foo

Tay

Siew

et al. 2011

Antimicrob Agents Chemother

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Mycobacterium tuberculosis is the causative agent of a pulmonary epidemic that is estimated to infect one-third of the world's population and that has an increased incidence of multidrug resistance. The evaluation of new chemical entities against M. tuberculosis is hampered by the lack of biological tools to help predict efficacy, from early drug development to clinical trials. As the rat is the animal species of choice in the pharmaceutical industry, we have developed a rat model of acute and chronic phases of M. tuberculosis infection for drug efficacy testing. In this model, we have evaluated the impact of tuberculosis drugs on T cell response using the enzyme-linked immunospot assay methodology. Infected rats treated with isoniazid (INH) or rifampin (RIF) responded to therapy, the potency of which was comparable to that seen in the mouse. Peripheral blood mononuclear cells from infected rats produced gamma interferon (IFN-␥) in response to RD-1 antigens, such as the 6-kDa early secretory antigen target (ESAT-6) and the 10-kDa culture filtrate protein (CFP-10). A decrease in IFN-␥ spot-forming cells (SFCs) was consistently observed in response to drug treatment. In both the acute-and chronic-phase models, the T cell response was more sensitive to ESAT-6 than to CFP-10. The SFC count in response to ESAT-6 appears to be an indicator of bacterial killing in the rat. Collectively, our data suggest that the ESAT-6 response could be used as a potential surrogate of drug efficacy in the rat and that such a readout could help shorten drug testing during preclinical development.Mycobacterium tuberculosis infection is among the world's leading infectious diseases, causing about 2 million deaths annually. The emergence of multidrug-resistant M. tuberculosis strains along with the increase of HIV coinfected cases worsens the situation (42). In countries with a high incidence of tuberculosis (TB), TB control programs rely on a diagnostic methods and drugs that have been developed decades ago and that are inadequate to effectively control the epidemic. The urgent need to develop new diagnostic tools as well as new therapeutic interventions is hampered by long clinical trials, where markers of infection and drug response are lacking (38).For decades, the tuberculin skin test (TST) has been used to diagnose TB (18). The TST measures cell-mediated immunity in the form of a delayed-type hypersensitivity response to the purified protein derivative (PPD), a crude mixture of antigens shared among M. tuberculosis, Mycobacterium bovis BCG, and several nontuberculous mycobacteria (NTM). As a result, the TST has lower specificity in populations with high BCG coverage and NTM exposure and shows poor sensitivity in immunocompromised individuals (30). The gamma interferon (IFN-␥) enzyme-linked immunospot (ELISpot) assay has emerged as an alternative to the TST. The assay consists of in vitro stimulation of peripheral blood mononuclear cells (PBMCs) using RD-1 antigens, the 6-kDa early secretory antigen target (ESAT-6) and the 10-kDa cul...

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Region of Difference 1 Antigen–Specific CD4⁺Memory T Cells Correlate with a Favorable Outcome of Tuberculosis

Abstract: These data suggest a protective role for RD1 peptide-specific CD4+ effector T cells, which undergo clonal expansion during Mycobacterium tuberculosis replication and then a contraction phase after disease resolution, culminating in the generation of CD4+ memory T cells.

Cited by 117 publications

References 30 publications

LTBI: latent tuberculosis infection or lasting immune responses toM. tuberculosis? A TBNET consensus statement

LTBI: latent tuberculosis infection or lasting immune responses toM. tuberculosis? A TBNET consensus statement

The risk of tuberculosis in transplant candidates and recipients: a TBNET consensus statement

T Cell Monitoring of Chemotherapy in Experimental Rat Tuberculosis

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Region of Difference 1 Antigen–Specific CD4+Memory T Cells Correlate with a Favorable Outcome of Tuberculosis

Abstract: These data suggest a protective role for RD1 peptide-specific CD4+ effector T cells, which undergo clonal expansion during Mycobacterium tuberculosis replication and then a contraction phase after disease resolution, culminating in the generation of CD4+ memory T cells.

Cited by 117 publications

References 30 publications

LTBI: latent tuberculosis infection or lasting immune responses toM. tuberculosis? A TBNET consensus statement

LTBI: latent tuberculosis infection or lasting immune responses toM. tuberculosis? A TBNET consensus statement

The risk of tuberculosis in transplant candidates and recipients: a TBNET consensus statement

T Cell Monitoring of Chemotherapy in Experimental Rat Tuberculosis

Contact Info

Product

Resources

About

Region of Difference 1 Antigen–Specific CD4⁺Memory T Cells Correlate with a Favorable Outcome of Tuberculosis