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Expansion of parasite-specific CD4+ and CD8+ T cells expressing IL-10 superfamily cytokine members and their regulation in human lymphatic filariasis.

Anuradha R, George PJ, Hanna LE, Kumaran P, Chandrasekaran V, Nutman TB, Babu S - PLoS Negl Trop Dis (2014)

Bottom Line: This CD4+ T cell expression pattern was associated with increased production of IL-19 and IL-24 by filarial-antigen stimulated PBMC.Interestingly, IL-10 blockade resulted in diminished frequencies of IL-19+ and IL-24+ T cells, whereas the addition of recombinant IL-10 resulted in significantly increased frequency of IL-19+ and IL-24+ T cells as well as significantly up regulated IL-19 and IL-24 gene expression, suggesting that IL-10 regulates IL-19 and IL-24 expression in T cells.In addition, IL-1β and IL-23 blockade also induced a diminution in the frequency of IL-19+ and IL-24+ T cells, indicating a novel role for these cytokines in the induction of IL-19 and IL-24 expressing T cells.

View Article: PubMed Central - PubMed

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

ABSTRACT

Background: Lymphatic filariasis (LF) is known to be associated with an increased production of IL-10. The role of the other IL-10 family members in the pathogenesis of infection and/or disease is not known.

Methodology/principal findings: We examined the expression patterns of IL-10 family members--IL-19, IL-24 and IL-26 in LF. We demonstrate that both CD4+ and CD8+ T cells express IL-19, IL-24 and IL-26 and that the frequency of CD4+ T cells expressing IL-19 and IL-24 (as well as IL-10) is significantly increased at baseline and following filarial antigen stimulation in patients with LF in comparison to individuals with filarial lymphedema and uninfected individuals. This CD4+ T cell expression pattern was associated with increased production of IL-19 and IL-24 by filarial-antigen stimulated PBMC. Moreover, the frequency of CD4+ and CD8+ T cells expressing IL-26 was significantly increased following filarial antigen stimulation in filarial lymphedema individuals. Interestingly, IL-10 blockade resulted in diminished frequencies of IL-19+ and IL-24+ T cells, whereas the addition of recombinant IL-10 resulted in significantly increased frequency of IL-19+ and IL-24+ T cells as well as significantly up regulated IL-19 and IL-24 gene expression, suggesting that IL-10 regulates IL-19 and IL-24 expression in T cells. In addition, IL-1β and IL-23 blockade also induced a diminution in the frequency of IL-19+ and IL-24+ T cells, indicating a novel role for these cytokines in the induction of IL-19 and IL-24 expressing T cells. Finally, elimination of infection resulted in significantly decreased frequencies of antigen - specific CD4+ T cells expressing IL-10, IL-19 and IL-24.

Conclusions: Our findings, therefore, suggest that IL-19 and IL-24 are associated with the regulation of immune responses in active filarial infection and potentially with protection against development of pathology, while IL-26 is predominantly associated with pathology in LF.

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Related in: MedlinePlus

Filarial infection is associated with increased frequencies of IL-10, IL-19 and IL-24 expressing and decreased frequencies of IL-26 expressing CD4+ T cells.(A) A representative dot plot from a filarial - infected individual showing CD4+ T cell expression of IL-10, IL-19, IL-24 and IL-26 in response to BmA and PMA/Ionomycin and representative dot plots from CP, INF and UN individuals for CD4+ T cell expression of IL-19 and IL-24. The frequencies of CD4+ T cells expressing IL-10 (B), IL-19 (C), IL-24 (D) and IL-26 (E) at baseline and following stimulation with BmA, Mf, PPD and PMA/ionomycin in CP (n = 23), INF (n = 25) and UN (n = 15) individuals. Antigen – stimulated frequencies are shown as net frequencies with the baseline levels subtracted. The data are shown as scatter plots with each circle representing a single individual. P values were calculated using the Kruskal-Wallis test with Dunn's multiple comparisons (* p<0.05, ** p<0.01, *** p<0.001).
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pntd-0002762-g001: Filarial infection is associated with increased frequencies of IL-10, IL-19 and IL-24 expressing and decreased frequencies of IL-26 expressing CD4+ T cells.(A) A representative dot plot from a filarial - infected individual showing CD4+ T cell expression of IL-10, IL-19, IL-24 and IL-26 in response to BmA and PMA/Ionomycin and representative dot plots from CP, INF and UN individuals for CD4+ T cell expression of IL-19 and IL-24. The frequencies of CD4+ T cells expressing IL-10 (B), IL-19 (C), IL-24 (D) and IL-26 (E) at baseline and following stimulation with BmA, Mf, PPD and PMA/ionomycin in CP (n = 23), INF (n = 25) and UN (n = 15) individuals. Antigen – stimulated frequencies are shown as net frequencies with the baseline levels subtracted. The data are shown as scatter plots with each circle representing a single individual. P values were calculated using the Kruskal-Wallis test with Dunn's multiple comparisons (* p<0.05, ** p<0.01, *** p<0.001).

Mentions: To determine the association of IL-10 and the related family members IL-19, IL-24 and IL-26 in protection from pathology and in susceptibility to or resistance to clinically apparent disease in LF, we measured the frequency of CD4+ T cells expressing these cytokines in INF individuals and in those with LF-associated disease (CP) or UN individuals (Figure 1A). As shown in Figure 1B, INF individuals had significantly increased frequencies of CD4+ T cells expressing IL-10 at homeostasis/steady state in comparison to CP individuals and increased frequencies of CD4+ T cells expressing IL-10 upon filarial antigen stimulation compared to CP and UN individuals. Similarly, INF individuals also exhibited significantly increased frequencies of CD4+ T cells expressing IL-19 at baseline in comparison to CP individuals and following filarial antigen stimulation compared to CP and UN individuals (Figure 1C). In addition, INF had significantly increased frequencies of CD4+ T cells expressing IL-24 at baseline and following filarial antigen stimulation in comparison to CP individuals (Figure 1D). In contrast, INF had significantly lower frequencies of CD4+ T cells expressing IL-26 following filarial antigen stimulation compared to CP individuals (Figure 1E). Interestingly, no significant difference was observed in the frequency of CD4+ T cells expressing IL-10, IL-19, IL-24 or IL-26 upon PPD stimulation or following PMA/ionomycin stimulation. Thus, filarial infection is associated with elevated frequencies of spontaneous and/or antigen – specific IL-10, IL-19 and IL-24 expressing CD4+ T cells in comparison to CP individuals, suggesting that these cells are associated with protection against pathology. In addition, filarial infection is also associated with decreased frequencies of antigen – specific IL-26 expressing CD4+ T cells in comparison to CP individuals, suggesting that IL-26 expressing T cells are pre-dominantly associated with pathology.


Expansion of parasite-specific CD4+ and CD8+ T cells expressing IL-10 superfamily cytokine members and their regulation in human lymphatic filariasis.

Anuradha R, George PJ, Hanna LE, Kumaran P, Chandrasekaran V, Nutman TB, Babu S - PLoS Negl Trop Dis (2014)

Filarial infection is associated with increased frequencies of IL-10, IL-19 and IL-24 expressing and decreased frequencies of IL-26 expressing CD4+ T cells.(A) A representative dot plot from a filarial - infected individual showing CD4+ T cell expression of IL-10, IL-19, IL-24 and IL-26 in response to BmA and PMA/Ionomycin and representative dot plots from CP, INF and UN individuals for CD4+ T cell expression of IL-19 and IL-24. The frequencies of CD4+ T cells expressing IL-10 (B), IL-19 (C), IL-24 (D) and IL-26 (E) at baseline and following stimulation with BmA, Mf, PPD and PMA/ionomycin in CP (n = 23), INF (n = 25) and UN (n = 15) individuals. Antigen – stimulated frequencies are shown as net frequencies with the baseline levels subtracted. The data are shown as scatter plots with each circle representing a single individual. P values were calculated using the Kruskal-Wallis test with Dunn's multiple comparisons (* p<0.05, ** p<0.01, *** p<0.001).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3974669&req=5

pntd-0002762-g001: Filarial infection is associated with increased frequencies of IL-10, IL-19 and IL-24 expressing and decreased frequencies of IL-26 expressing CD4+ T cells.(A) A representative dot plot from a filarial - infected individual showing CD4+ T cell expression of IL-10, IL-19, IL-24 and IL-26 in response to BmA and PMA/Ionomycin and representative dot plots from CP, INF and UN individuals for CD4+ T cell expression of IL-19 and IL-24. The frequencies of CD4+ T cells expressing IL-10 (B), IL-19 (C), IL-24 (D) and IL-26 (E) at baseline and following stimulation with BmA, Mf, PPD and PMA/ionomycin in CP (n = 23), INF (n = 25) and UN (n = 15) individuals. Antigen – stimulated frequencies are shown as net frequencies with the baseline levels subtracted. The data are shown as scatter plots with each circle representing a single individual. P values were calculated using the Kruskal-Wallis test with Dunn's multiple comparisons (* p<0.05, ** p<0.01, *** p<0.001).
Mentions: To determine the association of IL-10 and the related family members IL-19, IL-24 and IL-26 in protection from pathology and in susceptibility to or resistance to clinically apparent disease in LF, we measured the frequency of CD4+ T cells expressing these cytokines in INF individuals and in those with LF-associated disease (CP) or UN individuals (Figure 1A). As shown in Figure 1B, INF individuals had significantly increased frequencies of CD4+ T cells expressing IL-10 at homeostasis/steady state in comparison to CP individuals and increased frequencies of CD4+ T cells expressing IL-10 upon filarial antigen stimulation compared to CP and UN individuals. Similarly, INF individuals also exhibited significantly increased frequencies of CD4+ T cells expressing IL-19 at baseline in comparison to CP individuals and following filarial antigen stimulation compared to CP and UN individuals (Figure 1C). In addition, INF had significantly increased frequencies of CD4+ T cells expressing IL-24 at baseline and following filarial antigen stimulation in comparison to CP individuals (Figure 1D). In contrast, INF had significantly lower frequencies of CD4+ T cells expressing IL-26 following filarial antigen stimulation compared to CP individuals (Figure 1E). Interestingly, no significant difference was observed in the frequency of CD4+ T cells expressing IL-10, IL-19, IL-24 or IL-26 upon PPD stimulation or following PMA/ionomycin stimulation. Thus, filarial infection is associated with elevated frequencies of spontaneous and/or antigen – specific IL-10, IL-19 and IL-24 expressing CD4+ T cells in comparison to CP individuals, suggesting that these cells are associated with protection against pathology. In addition, filarial infection is also associated with decreased frequencies of antigen – specific IL-26 expressing CD4+ T cells in comparison to CP individuals, suggesting that IL-26 expressing T cells are pre-dominantly associated with pathology.

Bottom Line: This CD4+ T cell expression pattern was associated with increased production of IL-19 and IL-24 by filarial-antigen stimulated PBMC.Interestingly, IL-10 blockade resulted in diminished frequencies of IL-19+ and IL-24+ T cells, whereas the addition of recombinant IL-10 resulted in significantly increased frequency of IL-19+ and IL-24+ T cells as well as significantly up regulated IL-19 and IL-24 gene expression, suggesting that IL-10 regulates IL-19 and IL-24 expression in T cells.In addition, IL-1β and IL-23 blockade also induced a diminution in the frequency of IL-19+ and IL-24+ T cells, indicating a novel role for these cytokines in the induction of IL-19 and IL-24 expressing T cells.

View Article: PubMed Central - PubMed

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

ABSTRACT

Background: Lymphatic filariasis (LF) is known to be associated with an increased production of IL-10. The role of the other IL-10 family members in the pathogenesis of infection and/or disease is not known.

Methodology/principal findings: We examined the expression patterns of IL-10 family members--IL-19, IL-24 and IL-26 in LF. We demonstrate that both CD4+ and CD8+ T cells express IL-19, IL-24 and IL-26 and that the frequency of CD4+ T cells expressing IL-19 and IL-24 (as well as IL-10) is significantly increased at baseline and following filarial antigen stimulation in patients with LF in comparison to individuals with filarial lymphedema and uninfected individuals. This CD4+ T cell expression pattern was associated with increased production of IL-19 and IL-24 by filarial-antigen stimulated PBMC. Moreover, the frequency of CD4+ and CD8+ T cells expressing IL-26 was significantly increased following filarial antigen stimulation in filarial lymphedema individuals. Interestingly, IL-10 blockade resulted in diminished frequencies of IL-19+ and IL-24+ T cells, whereas the addition of recombinant IL-10 resulted in significantly increased frequency of IL-19+ and IL-24+ T cells as well as significantly up regulated IL-19 and IL-24 gene expression, suggesting that IL-10 regulates IL-19 and IL-24 expression in T cells. In addition, IL-1β and IL-23 blockade also induced a diminution in the frequency of IL-19+ and IL-24+ T cells, indicating a novel role for these cytokines in the induction of IL-19 and IL-24 expressing T cells. Finally, elimination of infection resulted in significantly decreased frequencies of antigen - specific CD4+ T cells expressing IL-10, IL-19 and IL-24.

Conclusions: Our findings, therefore, suggest that IL-19 and IL-24 are associated with the regulation of immune responses in active filarial infection and potentially with protection against development of pathology, while IL-26 is predominantly associated with pathology in LF.

Show MeSH
Related in: MedlinePlus