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Increased frequency of CD4+ CD25+ FoxP3+ T regulatory cells in pulmonary tuberculosis patients undergoing specific treatment and its relationship with their immune-endocrine profile.

Díaz A, Santucci N, Bongiovanni B, D'Attilio L, Massoni C, Lioi S, Radcliffe S, Dídoli G, Bottasso O, Bay ML - J Immunol Res (2015)

Bottom Line: While IL-6, IFN-γ, TGF-β (ELISA), and Cortisol (electrochemiluminescence, EQ) were augmented, DHEA-S (EQ) levels were diminished at T0 with respect to HCo, with cytokines and Cortisol returning to normal values at T9.Tregs correlated positively with IFN-γ (R = 0.868, P < 0.05) at T2 and negatively at T4 (R = -0.795, P < 0.05).Lowered levels of proinflammatory cytokines together with an increased frequency of Tregs of patients undergoing specific treatment might reflect a downmodulatory effect of these cells on the accompanying inflammation.

View Article: PubMed Central - PubMed

Affiliation: Institute of Immunology, School of Medical Sciences, National University of Rosario, Rosario, Santa Fe, Argentina.

ABSTRACT
Tuberculosis (TB) is a major health problem requiring an appropriate cell immune response (IR) to be controlled. Since regulatory T cells (Tregs) are relevant in IR regulation, we analyzed Tregs variations throughout the course of TB treatment and its relationship with changes in immune-endocrine mediators dealing with disease immunopathology. The cohort was composed of 41 adult patients, 20 of them completing treatment and follow-up. Patients were bled at diagnosis (T0) and at 2 (T2), 4 (T4), 6 (T6), and 9 months following treatment initiation. Twenty-four age- and sex-matched healthy controls (HCo) were also included. Tregs (flow cytometry) from TB patients were increased at T0 (versus HCo P < 0.05), showing even higher values at T2 (versus T0 P < 0.01) and T4 (versus T0 P < 0.001). While IL-6, IFN-γ, TGF-β (ELISA), and Cortisol (electrochemiluminescence, EQ) were augmented, DHEA-S (EQ) levels were diminished at T0 with respect to HCo, with cytokines and Cortisol returning to normal values at T9. Tregs correlated positively with IFN-γ (R = 0.868, P < 0.05) at T2 and negatively at T4 (R = -0.795, P < 0.05). Lowered levels of proinflammatory cytokines together with an increased frequency of Tregs of patients undergoing specific treatment might reflect a downmodulatory effect of these cells on the accompanying inflammation.

No MeSH data available.


Related in: MedlinePlus

CD4+CD25+FoxP3+ T cells (Tregs) frequency in TB patients. (a) Plot of cytometric analysis from a representative sample: (I) FSC and SSC identifying mononuclear cells, (II) CD4+ cells within the lymphocyte gate, (III) assessment of FoxP3+ cells gated on the CD4+ cells as shown in panel II, (IV) isotype control from the same sample, and (V) an additional control showing that the CD4+FoxP3+ population is also CD25 high. (b) Treg % comparisons between HCo and TB. (c) Comparisons of disease severity of TB patients. Box plots show median values, 25–75 percentiles of data in each group with maximum and minimum values. HCo: healthy controls.
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fig1: CD4+CD25+FoxP3+ T cells (Tregs) frequency in TB patients. (a) Plot of cytometric analysis from a representative sample: (I) FSC and SSC identifying mononuclear cells, (II) CD4+ cells within the lymphocyte gate, (III) assessment of FoxP3+ cells gated on the CD4+ cells as shown in panel II, (IV) isotype control from the same sample, and (V) an additional control showing that the CD4+FoxP3+ population is also CD25 high. (b) Treg % comparisons between HCo and TB. (c) Comparisons of disease severity of TB patients. Box plots show median values, 25–75 percentiles of data in each group with maximum and minimum values. HCo: healthy controls.

Mentions: Table 1 shows some general characteristics of study groups. All patients showed a decreased Body Mass Index (BMI) (P < 0.001). There were no differences with respect to age, sex distribution, BCG-vaccination, and peripheral CD8+ T cells frequency. However, we found that TB patients presented a significant diminution in CD4+ T cell levels (P < 0.05). Then we investigated whether active TB was associated with a CD4+CD25+FoxP3+ Treg expansion by assessing their frequency in PBMC of TB patients at the time of diagnosis by flow cytometry (Figure 1(a)). Results depicted in Figure 1(b) indicate that the frequency of Treg cells within the total CD4+ population was significantly increased in TB patients compared with HCo (P < 0.05). We next analyzed the percentage of Treg cells in TB patients according to their severity. As seen in Figure 1(c), moderate TB patients differed from HCo.


Increased frequency of CD4+ CD25+ FoxP3+ T regulatory cells in pulmonary tuberculosis patients undergoing specific treatment and its relationship with their immune-endocrine profile.

Díaz A, Santucci N, Bongiovanni B, D'Attilio L, Massoni C, Lioi S, Radcliffe S, Dídoli G, Bottasso O, Bay ML - J Immunol Res (2015)

CD4+CD25+FoxP3+ T cells (Tregs) frequency in TB patients. (a) Plot of cytometric analysis from a representative sample: (I) FSC and SSC identifying mononuclear cells, (II) CD4+ cells within the lymphocyte gate, (III) assessment of FoxP3+ cells gated on the CD4+ cells as shown in panel II, (IV) isotype control from the same sample, and (V) an additional control showing that the CD4+FoxP3+ population is also CD25 high. (b) Treg % comparisons between HCo and TB. (c) Comparisons of disease severity of TB patients. Box plots show median values, 25–75 percentiles of data in each group with maximum and minimum values. HCo: healthy controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4417597&req=5

fig1: CD4+CD25+FoxP3+ T cells (Tregs) frequency in TB patients. (a) Plot of cytometric analysis from a representative sample: (I) FSC and SSC identifying mononuclear cells, (II) CD4+ cells within the lymphocyte gate, (III) assessment of FoxP3+ cells gated on the CD4+ cells as shown in panel II, (IV) isotype control from the same sample, and (V) an additional control showing that the CD4+FoxP3+ population is also CD25 high. (b) Treg % comparisons between HCo and TB. (c) Comparisons of disease severity of TB patients. Box plots show median values, 25–75 percentiles of data in each group with maximum and minimum values. HCo: healthy controls.
Mentions: Table 1 shows some general characteristics of study groups. All patients showed a decreased Body Mass Index (BMI) (P < 0.001). There were no differences with respect to age, sex distribution, BCG-vaccination, and peripheral CD8+ T cells frequency. However, we found that TB patients presented a significant diminution in CD4+ T cell levels (P < 0.05). Then we investigated whether active TB was associated with a CD4+CD25+FoxP3+ Treg expansion by assessing their frequency in PBMC of TB patients at the time of diagnosis by flow cytometry (Figure 1(a)). Results depicted in Figure 1(b) indicate that the frequency of Treg cells within the total CD4+ population was significantly increased in TB patients compared with HCo (P < 0.05). We next analyzed the percentage of Treg cells in TB patients according to their severity. As seen in Figure 1(c), moderate TB patients differed from HCo.

Bottom Line: While IL-6, IFN-γ, TGF-β (ELISA), and Cortisol (electrochemiluminescence, EQ) were augmented, DHEA-S (EQ) levels were diminished at T0 with respect to HCo, with cytokines and Cortisol returning to normal values at T9.Tregs correlated positively with IFN-γ (R = 0.868, P < 0.05) at T2 and negatively at T4 (R = -0.795, P < 0.05).Lowered levels of proinflammatory cytokines together with an increased frequency of Tregs of patients undergoing specific treatment might reflect a downmodulatory effect of these cells on the accompanying inflammation.

View Article: PubMed Central - PubMed

Affiliation: Institute of Immunology, School of Medical Sciences, National University of Rosario, Rosario, Santa Fe, Argentina.

ABSTRACT
Tuberculosis (TB) is a major health problem requiring an appropriate cell immune response (IR) to be controlled. Since regulatory T cells (Tregs) are relevant in IR regulation, we analyzed Tregs variations throughout the course of TB treatment and its relationship with changes in immune-endocrine mediators dealing with disease immunopathology. The cohort was composed of 41 adult patients, 20 of them completing treatment and follow-up. Patients were bled at diagnosis (T0) and at 2 (T2), 4 (T4), 6 (T6), and 9 months following treatment initiation. Twenty-four age- and sex-matched healthy controls (HCo) were also included. Tregs (flow cytometry) from TB patients were increased at T0 (versus HCo P < 0.05), showing even higher values at T2 (versus T0 P < 0.01) and T4 (versus T0 P < 0.001). While IL-6, IFN-γ, TGF-β (ELISA), and Cortisol (electrochemiluminescence, EQ) were augmented, DHEA-S (EQ) levels were diminished at T0 with respect to HCo, with cytokines and Cortisol returning to normal values at T9. Tregs correlated positively with IFN-γ (R = 0.868, P < 0.05) at T2 and negatively at T4 (R = -0.795, P < 0.05). Lowered levels of proinflammatory cytokines together with an increased frequency of Tregs of patients undergoing specific treatment might reflect a downmodulatory effect of these cells on the accompanying inflammation.

No MeSH data available.


Related in: MedlinePlus