CD27low CD4 T Lymphocytes That Accumulate in the Mouse Lungs during Mycobacterial Infection Differentiate from CD27high Precursors In Situ, Produce IFN-γ, and Protect the Host against Tuberculosis Infection

Kapina, Marina A.; Shepelkova, Galina; Mischenko, Vladimir V.; Sayles, Peter C.; Bogacheva, P. O.; Winslow, Gary M.; Апт, А. С.; Lyadova, Irina V.

doi:10.4049/jimmunol.178.2.976

Cited by 43 publications

(55 citation statements)

References 52 publications

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“…CD27 downregulation seems to be part of a functional program rather than the result of interaction with CD70 (43). Memory CD4 ϩ T cells at tissue sites also display this phenotype (44). Its functional significance is presently difficult to envision, but it suggests a particular relevance of CD27/CD70 interactions for T cells at the tissue site, in line with data gathered from CD27 Ϫ/Ϫ mice (36).…”

Section: Discussionsupporting

confidence: 61%

CD27 Instructs CD4+ T Cells to Provide Help for the Memory CD8+ T Cell Response after Protein Immunization

Xiao

Peperzak

Keller

et al. 2008

The Journal of Immunology

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For optimal quality, memory CD8+ T cells require CD4+ T cell help. We have examined whether CD4+ T cells require CD27 to deliver this help, in a model of intranasal OVA protein immunization. CD27 deficiency reduced the capacity of CD4+ T cells to support Ag-specific CD8+ T cell accumulation at the tissue site after primary and secondary immunization. CD27-dependent CD4+ T cell help for the memory CD8+ T cell response was delivered during priming. It did not detectably affect formation of CD8+ memory T cells, but promoted their secondary expansion. CD27 improved survival of primed CD4+ T cells, but its contribution to the memory CD8+ T cell response relied on altered CD4+ T cell quality rather than quantity. CD27 induced a Th1-diagnostic gene expression profile in CD4+ T cells, which included the membrane molecule MS4A4B. Accordingly, CD27 increased the frequency of IFN-γ- and IL-2-producing CD4+ T cells. It did not affect CD40L expression. Strikingly, MS4A4B was also identified as a unique marker of CD8+ memory T cells that had received CD27-proficient CD4+ T cell help during the primary response. This apparent imprinting effect suggests a role for MS4A4B as a downstream effector in CD27-dependent help for CD8+ T cell memory.

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Section: Discussionsupporting

confidence: 61%

CD27 Instructs CD4+ T Cells to Provide Help for the Memory CD8+ T Cell Response after Protein Immunization

Xiao

Peperzak

Keller

et al. 2008

The Journal of Immunology

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“…CD27 À CD62L lo CD4 1 T cells have been reported to accumulate in lungs during murine MTB infection and secrete high levels of IFN-g [23]. In WT mice, bulk CD4 1 and CD8 1 T cells, as well as antigen-specific CD8 1 T cells, from lung down-regulated CD27 over the course of MTB infection ( Fig.…”

Section: Normal T-cell Development Without Slomentioning

confidence: 99%

Secondary lymphoid organs are dispensable for the development of T‐cell‐mediated immunity during tuberculosis

et al. 2010

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Tuberculosis causes 2 million deaths per year, yet in most cases the immune response successfully contains the infection and prevents disease outbreak. Induced lymphoid structures associated with pulmonary granuloma are observed during tuberculosis in both humans and mice and could orchestrate host defense. To investigate whether granuloma perform lymphoid functions, mice lacking secondary lymphoid organs (SLO) were infected with Mycobacterium tuberculosis (MTB). As in WT mice, granuloma developed, exponential growth of MTB was controlled, and antigen-specific T-cell responses including memory T cells were generated in the absence of SLO. Moreover, adoptively transferred T cells were primed locally in lungs in a granuloma-dependent manner. T-cell activation was delayed in the absence of SLO, but resulted in a normal development program including protective subsets and functional recall responses that protected mice against secondary MTB infection. Our data demonstrate that protective immune responses can be generated independently of SLO during MTB infection and implicate local pulmonary T-cell priming as a mechanism contributing to host defense.Key words: Granuloma . Lymphoid neogenesis . T-cell development . Tuberculosis Supporting Information available online IntroductionMycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB), currently persists in one-third of the world's population [1]. In most cases, the immune response generated upon exposure contains, but does not eradicate, the bacilli and an asymptomatic persistent infection develops, termed latent TB. Approximately one in ten latently infected individuals undergo reactivation to active TB disease during their lifetime. However, Ã These authors contributed equally to this work. ÃÃ These authors share equal senior authorship. [2,3]. Granuloma are considered central for control of MTB as loss of granuloma structure is associated with poor disease outcome in humans and animal models [3,4]. Yet, the precise mechanisms by which granuloma mediate control of MTB are poorly understood. Induction of an adaptive immune response is essential for host protection against MTB. Antigen-specific T-cell responses are generated within secondary lymphoid organs (SLO), such as lymph nodes (NO) and spleen. SLO maximize efficiency of encounters between APC and naïve T lymphocytes [5]. Therefore, SLO are critical for the generation of adaptive immunity. Ectopic accumulations of lymphoid cells, known as tertiary lymphoid organs, sometimes arise during chronic inflammation or infection. Tertiary lymphoid organs resemble SLO in structure and cell composition and evidence exists that some are capable of generating adaptive immunity [5,6]. However, whether immune responses generated outside of SLO are truly effective and thus beneficial in defense against pathogens is unclear.Recent reports have described lymphoid features associated with murine and human granuloma, such as B-cell follicles and the peripheral node addressin, which is expressed on high endothel...

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“…CD27 is widely used as a marker of memory B cells in humans [22]. Studies in a TB mouse model and pulmonary TB patients have shown a reduced level of CD27 expression on antigenspecific CD41 T cells associated with the persistence of active TB, suggesting a high ratio of fully differentiated effector CD4 1 T cells and the presence of antigens in vivo [23,24]. Similarly, Figure 7.…”

mentioning

confidence: 99%

B lymphocytes that migrate to tuberculous pleural fluid via the SDF‐1/CXCR4 axis actively respond to antigens specific for Mycobacterium tuberculosis

Feng

Liu

et al. 2011

Eur J Immunol

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B-cell biology has been largely uncharacterized in the field of tuberculosis (TB). In this study, we investigated the immunophenotypical and functional characteristics of B cells obtained from the pleural fluid (PF) and peripheral blood of patients with tuberculous pleuritis (TP). Our results indicated that the total numbers of B cells, CD271 memory B cells and plasmablasts were clearly lower in the PF than in peripheral blood. Furthermore, we found significantly higher expression of CXCR4 on B cells in the PF, and a chemotaxis assay showed that B cells in the PF were more responsive to stromal cell-derived factor-1 (SDF-1) than B cells from peripheral blood. In addition, SDF-1 levels in PF were remarkably high compared with SDF-1 levels in plasma, suggesting that the SDF-1/CXCR4 axis might facilitate the migration of circulating B cells into tuberculous pleural space. Importantly, we observed that significantly more antibodies were produced by B cells in the PF following stimulation with BCG, early secretory antigenic target (ESAT-6)/culture filtrate protein-10 (CFP-10) or ESAT-6 protein.Collectively, these data demonstrate that Mycobacterium tuberculosis-specific B cells exist at local sites of infection in TP patients and this localization might influence the immune response to M. tuberculosis. Key words: B cells . Chemokine receptors . Immune responses . Tuberculous pleuritis Supporting Information available onlineIntroduction Tuberculosis (TB), one of the oldest infectious diseases associated with humans, is a chronic disease caused by infection with Mycobacterium tuberculosis [1,2]. The incidence of TB has increased during the past 20 years for reasons such as insufficient prevention efforts, incorrectly prescribed medication, the emergence of drug-resistant strains of M. tuberculosis and the prevalence of human immunodeficiency virus (HIV) infection [3,4]. Traditionally, the immune response against M. tuberculosis infection is dominated by cell-mediated immunity (CMI), which relies primarily on CD4 1 and CD8 1 T cells. Therefore, many studies have been conducted in an attempt to augment cellular immunity, with an aim to develop new vaccine candidates against TB [5][6][7]. In contrast to these investigations, the contribution of B cells and humoral immunity in the TB field remains largely unexamined and elusive. Fewer efforts to promote an effective humoral response against M. tuberculosis have been made compared with those devised to elicit a cellular response [8]. However, it is worth noting that any successful, novel vaccine strategy against TB will have to properly invoke both humoral and cellular immunity, given that these responses are the two critical arms of adaptive immunity and always collaborate to repel infectious pathogens [9]. Numerous murine studies have shown that B cells and antibodies have pleiotropic activities and display previously underappreciated roles during M. tuberculosis infection [10][11][12]. In contrast to the murine studies, there are limited data regarding any phenotypic and...

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CD27low CD4 T Lymphocytes That Accumulate in the Mouse Lungs during Mycobacterial Infection Differentiate from CD27high Precursors In Situ, Produce IFN-γ, and Protect the Host against Tuberculosis Infection

Cited by 43 publications

References 52 publications

CD27 Instructs CD4+ T Cells to Provide Help for the Memory CD8+ T Cell Response after Protein Immunization

CD27 Instructs CD4+ T Cells to Provide Help for the Memory CD8+ T Cell Response after Protein Immunization

Secondary lymphoid organs are dispensable for the development of T‐cell‐mediated immunity during tuberculosis

B lymphocytes that migrate to tuberculous pleural fluid via the SDF‐1/CXCR4 axis actively respond to antigens specific for Mycobacterium tuberculosis

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