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Decreased frequencies of circulating CD4⁺ T follicular helper cells associated with diminished plasma IL-21 in active pulmonary tuberculosis.

Kumar NP, Sridhar R, Hanna LE, Banurekha VV, Nutman TB, Babu S - PLoS ONE (2014)

Bottom Line: We found that both ex vivo and TB - antigen induced frequencies of Tfh cell subsets was significantly lower in PTB compared to LTB individuals.Similarly, antigen induced frequencies of Tfh cells expressing IL-21 was also significantly lower in PTB individuals and this was reflected in diminished circulating levels of IL-21 and IFNγ.Thus, PTB is characterized by adiminution in the frequency of Tfh cell subsets.

View Article: PubMed Central - PubMed

Affiliation: National Institutes of Health-International Center for Excellence in Research, Chennai, India; National Institute for Research in Tuberculosis, Chennai, India.

ABSTRACT

Background: Circulating T follicular helper (Tfh) cells represent a distinct subset of CD4+ T cells and are important in immunity to infections. Although they have been shown to play a role in experimental models of tuberculosis infection, their role in human tuberculosis remains unexplored.

Aims/methodology: To determine the distribution of circulating Tfh cells in human TB, we measured the frequencies of Tfh cells ex vivo and following TB - antigen or polyclonal stimulation in pulmonary TB (PTB; n = 30) and latent TB (LTB; n = 20) individuals, using the markers CXCR5, PD-1 and ICOS.

Results: We found that both ex vivo and TB - antigen induced frequencies of Tfh cell subsets was significantly lower in PTB compared to LTB individuals. Similarly, antigen induced frequencies of Tfh cells expressing IL-21 was also significantly lower in PTB individuals and this was reflected in diminished circulating levels of IL-21 and IFNγ. This was not accompanied by diminished frequencies of activated or memory B cell subsets. Finally, the diminution in frequency of Tfh cells in PTB individuals was dependent on IL-10, CTLA-4 and PD-L1 in vitro.

Conclusions: Thus, PTB is characterized by adiminution in the frequency of Tfh cell subsets.

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Related in: MedlinePlus

Diminished circulating IL-21 levels in PTB is associated with decreased spontaneous frequencies of Tfh subsets.(A) The circulating levels of Tfh associated cytokines - IL-21, IFNγ, IL-4 and IL-17 were measured by ELISA in PTB and LTB individuals. Results are shown as scatter plots with each circle representing a single individual. P values were calculated using the Mann-Whitney U test. (B) The correlation between circulating IL-21 levels and Tfh subsets in shown as scatter plots in PTB individuals. P values were calculated using Spearman rank correlation.
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pone-0111098-g004: Diminished circulating IL-21 levels in PTB is associated with decreased spontaneous frequencies of Tfh subsets.(A) The circulating levels of Tfh associated cytokines - IL-21, IFNγ, IL-4 and IL-17 were measured by ELISA in PTB and LTB individuals. Results are shown as scatter plots with each circle representing a single individual. P values were calculated using the Mann-Whitney U test. (B) The correlation between circulating IL-21 levels and Tfh subsets in shown as scatter plots in PTB individuals. P values were calculated using Spearman rank correlation.

Mentions: Since circulating Tfh cells are also known to produce - IFNγ, IL-4 and IL-17 in addition to IL-21 [12], we determined the circulating levels of these cytokines in PTB and LTB individuals. As shown in Figure 4A, PTB individuals exhibited significantly lower plasma levels of IL-21 and IFNγ but not IL-4 or IL-17 in comparison to LTB individuals. Interestingly, when we examined the relationship between the spontaneous frequencies of Tfh cell subsets and the circulating levels of IL-21, we observed a significant positive correlation between the frequencies of CD4+ CXCR5+ ICOS+ T cells and CD4+ CXCR5+ PD-1+ T cells and plasma levels of IL-21 (Figure 4B). No significant correlation was observed between the spontaneous frequencies of Tfh cell subsets and plasma levels of IFNγ (data not shown). Thus, diminished spontaneous frequencies of Tfh cells subsets is significantly and directly associated with diminished IL-21 levels in PTB.


Decreased frequencies of circulating CD4⁺ T follicular helper cells associated with diminished plasma IL-21 in active pulmonary tuberculosis.

Kumar NP, Sridhar R, Hanna LE, Banurekha VV, Nutman TB, Babu S - PLoS ONE (2014)

Diminished circulating IL-21 levels in PTB is associated with decreased spontaneous frequencies of Tfh subsets.(A) The circulating levels of Tfh associated cytokines - IL-21, IFNγ, IL-4 and IL-17 were measured by ELISA in PTB and LTB individuals. Results are shown as scatter plots with each circle representing a single individual. P values were calculated using the Mann-Whitney U test. (B) The correlation between circulating IL-21 levels and Tfh subsets in shown as scatter plots in PTB individuals. P values were calculated using Spearman rank correlation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4208798&req=5

pone-0111098-g004: Diminished circulating IL-21 levels in PTB is associated with decreased spontaneous frequencies of Tfh subsets.(A) The circulating levels of Tfh associated cytokines - IL-21, IFNγ, IL-4 and IL-17 were measured by ELISA in PTB and LTB individuals. Results are shown as scatter plots with each circle representing a single individual. P values were calculated using the Mann-Whitney U test. (B) The correlation between circulating IL-21 levels and Tfh subsets in shown as scatter plots in PTB individuals. P values were calculated using Spearman rank correlation.
Mentions: Since circulating Tfh cells are also known to produce - IFNγ, IL-4 and IL-17 in addition to IL-21 [12], we determined the circulating levels of these cytokines in PTB and LTB individuals. As shown in Figure 4A, PTB individuals exhibited significantly lower plasma levels of IL-21 and IFNγ but not IL-4 or IL-17 in comparison to LTB individuals. Interestingly, when we examined the relationship between the spontaneous frequencies of Tfh cell subsets and the circulating levels of IL-21, we observed a significant positive correlation between the frequencies of CD4+ CXCR5+ ICOS+ T cells and CD4+ CXCR5+ PD-1+ T cells and plasma levels of IL-21 (Figure 4B). No significant correlation was observed between the spontaneous frequencies of Tfh cell subsets and plasma levels of IFNγ (data not shown). Thus, diminished spontaneous frequencies of Tfh cells subsets is significantly and directly associated with diminished IL-21 levels in PTB.

Bottom Line: We found that both ex vivo and TB - antigen induced frequencies of Tfh cell subsets was significantly lower in PTB compared to LTB individuals.Similarly, antigen induced frequencies of Tfh cells expressing IL-21 was also significantly lower in PTB individuals and this was reflected in diminished circulating levels of IL-21 and IFNγ.Thus, PTB is characterized by adiminution in the frequency of Tfh cell subsets.

View Article: PubMed Central - PubMed

Affiliation: National Institutes of Health-International Center for Excellence in Research, Chennai, India; National Institute for Research in Tuberculosis, Chennai, India.

ABSTRACT

Background: Circulating T follicular helper (Tfh) cells represent a distinct subset of CD4+ T cells and are important in immunity to infections. Although they have been shown to play a role in experimental models of tuberculosis infection, their role in human tuberculosis remains unexplored.

Aims/methodology: To determine the distribution of circulating Tfh cells in human TB, we measured the frequencies of Tfh cells ex vivo and following TB - antigen or polyclonal stimulation in pulmonary TB (PTB; n = 30) and latent TB (LTB; n = 20) individuals, using the markers CXCR5, PD-1 and ICOS.

Results: We found that both ex vivo and TB - antigen induced frequencies of Tfh cell subsets was significantly lower in PTB compared to LTB individuals. Similarly, antigen induced frequencies of Tfh cells expressing IL-21 was also significantly lower in PTB individuals and this was reflected in diminished circulating levels of IL-21 and IFNγ. This was not accompanied by diminished frequencies of activated or memory B cell subsets. Finally, the diminution in frequency of Tfh cells in PTB individuals was dependent on IL-10, CTLA-4 and PD-L1 in vitro.

Conclusions: Thus, PTB is characterized by adiminution in the frequency of Tfh cell subsets.

Show MeSH
Related in: MedlinePlus