Increased Frequency of Regulatory T Cells and T Lymphocyte Activation in Persons with Previously Treated Extrapulmonary Tuberculosis

Almeida, Alexandre S. de; Fiske, Christina T.; Sterling, Timothy R.; Kalams, Spyros A.

doi:10.1128/cvi.05263-11

Cited by 41 publications

(39 citation statements)

References 53 publications

(69 reference statements)

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“…Our group has previously noted reduced peripheral blood mononuclear cell (PBMC) cytokine production and CD4 ϩ T lymphocytes in HIV-seronegative adults with previous extrapulmonary TB compared to persons with previous pulmonary TB or latent M. tuberculosis infection (2,38). In a subset of patients from the present study, we also found that persons with previous extrapulmonary TB had increased regulatory T cell frequency and CD4 ϩ lymphocyte activation, indicating possible immune dysregulation (8). However, an evaluation of the sequential activation of innate and adaptive immune responses to M. tuberculosis infection in such patients has not been performed.…”

supporting

confidence: 65%

“…IL-17 is a proinflammatory cytokine that participates in the early defense against M. tuberculosis infection and has been shown in murine models to be essential for granuloma formation (33). In a separate study that included a subset of the current study's patient population, we observed that persons with previous extrapulmonary TB have increased frequencies of regulatory T cells, a category of T cells characterized by surface expression of CD4 and CD25, and intracellular expression of FoxP3 (8). In active TB, regulatory T cells suppress IFN-␥ production but have less suppressive effects on IL-17 production (32).…”

Section: Discussionmentioning

confidence: 61%

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Abnormal Immune Responses in Persons with Previous Extrapulmonary Tuberculosis in anIn VitroModel That SimulatesIn VivoInfection with Mycobacterium tuberculosis

Fiske

Almeida

Shintani

et al. 2012

Clin. Vaccine Immunol.

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T uberculosis (TB) presents an interesting paradox: while onethird of the world's population is infected with Mycobacterium tuberculosis, only 5 to 10% of those infected will develop active disease (1,23). This observation suggests that factors other than the mycobacterium play a role in the development of TB. Our understanding of protective immunity to M. tuberculosis infection is incomplete. The immune response to M. tuberculosis involves cells such as monocytes, macrophages, and T lymphocytes that produce cytokines such as CXCL8 (interleukin-8 [IL-8]), IL-12, gamma interferon (IFN-␥), and tumor necrosis alpha (TNF-␣) (16). While hematogenous dissemination occurs in most persons soon after infection, subsequent extrapulmonary TB disease does not (25). Development of extrapulmonary disease could be a result of a breakdown in host immune surveillance, a change in the mycobacteria from a dormant to an active state, or a combination of the two. Discovery of factors that predispose to extrapulmonary disease will advance TB prevention efforts by identifying immune responses that could be boosted by TB vaccines. It will also help identify individuals at increased risk for progression from latent infection to clinical disease, so that more intensive observation and treatment of latent infection can be initiated.Extrapulmonary TB is associated with underlying immune defects. For example, HIV-infected persons are at increased risk of extrapulmonary TB, and this risk increases as the CD4 ϩ T lymphocyte count declines (30). Young children also have an increased incidence of extrapulmonary TB, specifically TB meningitis, presumably due to an immature immune system (31). Our group has previously noted reduced peripheral blood mononuclear cell (PBMC) cytokine production and CD4 ϩ T lymphocytes in HIV-seronegative adults with previous extrapulmonary TB compared to persons with previous pulmonary TB or latent M. tuberculosis infection (2, 38). In a subset of patients from the present study, we also found that persons with previous extrapulmonary TB had increased regulatory T cell frequency and CD4 ϩ lymphocyte activation, indicating possible immune dysregulation (8). However, an evaluation of the sequential activation of innate and adaptive immune responses to M. tuberculosis infection in such patients has not been performed. We therefore assessed in vitro immune responses in persons with previous extrapulmonary TB under several experimental conditions, including one in which autologous monocyte-depleted PBMCs were cocultured with M. tuberculosis-infected host macrophages.

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supporting

confidence: 65%

Section: Discussionmentioning

confidence: 61%

Abnormal Immune Responses in Persons with Previous Extrapulmonary Tuberculosis in anIn VitroModel That SimulatesIn VivoInfection with Mycobacterium tuberculosis

Fiske

Almeida

Shintani

et al. 2012

Clin. Vaccine Immunol.

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“…13,22,23 However, it is unclear whether 25(OH)D levels are different between PTB and EPTB. Only two prior case-control studies reported 25(OH)D levels in patients with EPTB.…”

Section: Discussionmentioning

confidence: 99%

25-Hydroxyvitamin D levels after recovery from tuberculosis: Insights into pathogenesis

2014

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Objective 25-hydroxyvitamin D [25(OH)D] levels after recovery from tuberculosis (TB) may reflect pre-morbid levels and therefore provide insight into pathogenesis. We assessed 25(OH)D levels after recovery from TB disease, and compared to levels in persons without TB disease. Methods Case-control study. Cases were persons who had recovered from culture-confirmed Mycobacterium tuberculosis disease. Controls were persons without TB disease. Total 25(OH)D was measured from stored plasma specimens using liquid chromatography-mass spectrometry. Results 29 persons with prior TB disease and 36 controls were included. Median 25(OH)D levels were 24.7 ng/mL (IQR, 18.3–34.1) in prior TB disease, and 33.6 ng/mL (IQR, 26.2–42.4) in controls (Mann-Whitney; P=0.01). Multivariable linear regression analysis showed that black race (adjusted mean difference [β]=−8.3 ng/mL; 95% CI −14.5, −2.2; P<0.01), enrollment in winter (β=−10.4 ng/mL; 95% CI −17.0, −3.8; P<0.01) and prior TB disease (β=−5.8 ng/mL; 95% CI −11.4, −0.3; P=0.05) were associated with lower 25(OH)D levels. Conclusions Persons who had recovered from TB disease had lower 25(OH)D levels compared to controls without TB disease, after adjusting for important confounders. Larger, longitudinal studies are needed to further characterize the possible role of low 25(OH)D in the pathogenesis of TB disease and TB recurrence after recovery.

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“…The finding of increased Treg numbers in active TB and their decline after chemotherapy indicated their association with the progression of disease (He et al, 2010). Higher numbers of Treg's (CD4 + CD25 hi CD12 7 low Foxp3 + ) were observed in the blood of patients with extrapulmonary compared to pulmonary TB (de Almeida et al, 2012).…”

Section: Sequestration Of Lymphoid Cells To Body Fluidsmentioning

confidence: 96%

Local Immune Responses in Tuberculosis

Iványi

2015

Mucosal Immunology

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Increased Frequency of Regulatory T Cells and T Lymphocyte Activation in Persons with Previously Treated Extrapulmonary Tuberculosis

Cited by 41 publications

References 53 publications

Abnormal Immune Responses in Persons with Previous Extrapulmonary Tuberculosis in anIn VitroModel That SimulatesIn VivoInfection with Mycobacterium tuberculosis

Abnormal Immune Responses in Persons with Previous Extrapulmonary Tuberculosis in anIn VitroModel That SimulatesIn VivoInfection with Mycobacterium tuberculosis

25-Hydroxyvitamin D levels after recovery from tuberculosis: Insights into pathogenesis

Local Immune Responses in Tuberculosis

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